Pain Management for Veterinary Technicians and Nurses [2 ed.] 1119892384, 9781119892380

Table of contents :
Cover
Title Page
Copyright Page
Contents
List of Contributors
Foreword
Acknowledgments
About the Companion Website
Chapter 1 Advancing Veterinary Pain Management into a New Era
1.1 Introduction
1.2 Brief History of Human Pain Management
1.3 Veterinary Pain Management Through the Centuries
1.4 Animal Research Contributions
1.5 History of Animal Nursing Staff
1.5.1 National Association of Veterinary Technicians in America Recognized Veterinary Technician Specialty Academies
1.6 Eyewitness to 50 Years of Changes for Veterinary Technicians
1.7 Veterinary Technician Pioneers in Pain Management
1.8 Future Directions for Veterinary Technician Pain Management
1.9 Conclusion
References
Chapter 2 Careers in Animal Pain Management
2.1 Introduction
2.2 Pain Management Certifications Available for Veterinary Technicians/Nurses
2.2.1 Certified Veterinary Pain Practitioner (CVPP)
2.2.2 Veterinary Technician Specialist (Anesthesia and Analgesia), and Veterinary Technician Specialist (Laboratory Animal Medicine – Research Anesthetist)
2.2.3 Veterinary Technician Specialist (Physical Rehabilitation)
2.2.4 Surgical Research Anesthetist (SRA)
2.2.5 The University of Tennessee Companion Animal Pain Management Certificate Program
2.2.6 AAHA Pain Management Guidelines Certificate Course (AAHA Pain Management Champion)
2.2.7 WSAVA Certificate in Pain Management
2.2.8 Canine Rehabilitation Veterinary Technician Certifications
2.2.9 Equine Rehabilitation Veterinary Technician Certifications
2.2.10 Certified Equine Massage Therapist
2.2.11 Animal Acupressure and Massage
2.2.12 TCVM Veterinary Technician Programs Offered by the Chi Institute
2.2.13 Animal Acupuncture
2.2.14 Low-Stress Certifications
2.2.15 Veterinary Anaesthesia and Analgesia (MSc), (PgDip), (PgCert), or (PgProfDev)
2.2.16 Canine Arthritis Management Practitioner (CAMP)
2.2.17 Certified Companion Animal Rehabilitation Therapist (CCAT)
2.3 Leveraging Veterinary Technicians in Pain Management
2.4 Conclusion
Chapter 3 Pain Physiology and Psychology
3.1 Introduction
3.2 What Is “Pain”
3.2.1 The Negative Effects of Pain
3.3 Breaking Down the Nociceptive Pathway
3.3.1 Transduction
3.3.2 Transmission
3.3.3 Modulation
3.3.4 Perception
3.3.5 The Dorsal Horn
3.3.6 Ventral Horn and Intermediate Zone
3.3.7 White Matter
3.3.8 Descending Pathways
3.3.9 Spinothalamic Tract
3.3.10 Spinoreticular Tract
3.3.11 Peripheral Sensitization
3.3.12 Central Sensitization
3.4 The Endocannabinoid System and Pain
3.5 The Gate Control Theory
3.6 Psychological Aspects of Pain
3.6.1 Personality and the Pain Experience
3.6.2 Stress and Anxiety on Pain
3.6.3 Pain Catastrophizing
3.6.4 Boredom and Pain
3.6.5 Neuroplasticity and the Memory of Pain
3.6.6 Caregiver Placebo
3.7 Types of Pain
3.7.1 Somatic, Visceral, and Referred Pain
3.7.2 Physiological/Adaptive/Acute Pain
3.7.3 Pathological/Maladaptive/Chronic Pain
3.7.4 Neuropathic Pain
3.7.5 Radicular Pain
3.7.6 Chronic/Persistent Postsurgical Pain
3.7.7 Complex Regional Pain Syndrome
3.7.8 Social Resilience and Pain
3.8 The Microbiome and Pain Pathophysiology
3.8.1 What Is a Microbiome?
3.8.2 Determining “Healthy” in a Microbiome
3.8.3 Gut Microbiome Imbalance or Dysbiosis
3.8.4 The Gut-Brain Axis
3.8.5 Microbial Derived Mediators
3.8.6 Pathogen-Associated Molecular Patterns (PAMPs)
3.8.7 Microbial-Derived Metabolites
3.8.8 Neurotransmitters or Neuromodulators
3.8.9 Endocannabinoid Axis
3.8.10 Pain Medication and the Microbiome
References
Chapter 4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species
4.1 Introduction
4.2 Pain Domains
4.2.1 Pain Intensity and Affect
4.2.2 Temporal Dimensions
4.2.3 Location and Bodily Distribution of Pain
4.3 Disposition and Personality
4.4 Breed or Species Bias
4.5 Dysphoria, Emergence Agitation, and Emergence Delirium
4.6 Placebo, Caregiver Placebo, and Placebo-by-Proxy
4.7 Non–species-specific Assessments
4.7.1 Quantitative Sensory Testing (QST)
4.7.2 Temporal Summation (TS)
4.7.3 Nociceptive Withdrawal Reflex (NWR)
4.7.4 Gait Analysis
4.7.5 Pain Biomarkers
4.7.6 Machine Learning and Artificial Intelligence (AI)
4.7.7 Activity Monitors (AMs)
4.7.8 Facial Expression or Grimace Scales
4.8 Clinical Pain Scoring Tools (Canine and Feline)
4.8.1 Canine Acute Pain Scoring
4.8.1.1 Glasgow Composite Measure Pain Scale – Short and Long Forms (CMPS) (Validated)
4.8.1.2 French Association for Animal Anesthesia and Analgesia Pain Scoring System (4A-Vet)(Validated)
4.8.1.3 University of Melbourne Pain Scale (UMPS) (Validated)
4.8.2 Canine Chronic Pain Scoring
4.8.2.1 Canine Brief Pain Inventory (CBPI) (Validated)
4.8.2.2 Helsinki Chronic Pain Index (HCPI) (Validated)
4.8.2.3 Liverpool Osteoarthritis in Dogs (LOAD) (Validated)
4.8.3 Feline Acute Pain Scoring
4.8.3.1 Glasgow Composite Measure Pain Scale-Short-Form (CMPS-SF) (Validated)
4.8.3.2 Feline Grimace Scale (FGS) (Validated)
4.8.4 Feline Chronic Pain Scoring
4.8.4.1 Client-specific Outcome Measures – Feline (CSOMf) (Validated)
4.8.4.2 Montreal Instrument for Cat Arthritis Testing-caretaker (MI-CAT-(c)) (Validated)
4.8.4.3 Feline Musculoskeletal Pain Index (FMPI) (Not Validated)
4.8.4.4 Oral Pain Scale – Canine/Feline (COPS–C/F) (Validated)
4.8.4.5 Cincinnati Orthopedic
4.8.4.6 HHHHHMM Scale (Not Validated)
4.8.4.7 VetMetrica™ Health-related Quality of Life (HRQoL) (Validated)
4.8.4.8 Food and Fiber Species Pain Recognition and Scoring
4.9 Bovids
4.9.1 Indications of Pain in Cattle
4.10 Small Ruminants and Camelids
4.11 Swine
4.11.1 Normal Behavioral Observations in Swine
4.12 Equid Pain Recognition and Scoring
4.12.1 Horses
4.12.1.1 Appearance of the Normal Horse
4.12.1.2 Somatic Pain Indicators
4.12.1.3 Signs of Laminitis Pain Vary with the Progression of the Disease
4.12.1.4 Visceral Pain Indicators
4.12.1.5 Horse Grimace Scale
4.12.2 Donkeys
4.13 Exotic Species Pain Recognition and Scoring
4.13.1 Birds
4.13.2 Appearance of a Non-painful Bird
4.13.3 Appearance of a Painful Bird
4.13.4 Developing a Pain Score in Birds
4.14 Reptiles
4.14.1 Appearance of a Nonpainful Reptile
4.14.2 Appearance of a Reptile in Pain
4.14.3 Developing a Pain Score in Reptiles
4.15 Amphibians and Fish
4.15.1 Appearance of a Nonpainful Fish and Amphibian
4.15.2 Appearance of a Painful Fish and Amphibian
4.15.3 Developing a Pain Scoring Assessments in Fish and Amphibians
4.16 Small Exotic Mammals
4.16.1 Appearance of Nonpainful Small Exotic Mammals
4.16.2 Appearance of Painful Small Exotic Mammals
4.16.3 Developing a Pain Score in Small Exotic Mammals
References
Chapter 5 Analgesia Pharmacology
5.1 Introduction
5.2 Definitions
5.3 Analgesic Drugs
5.4 Opioids
5.4.1 Full Opioid Agonists
5.4.2 Individual Drug Facts
5.4.2.1 Morphine
5.4.2.2 Meperidine (Pethidine)
5.4.2.3 Methadone
5.4.2.4 Hydromorphone
5.4.2.5 Oxymorphone
5.4.2.6 Fentanyl, Remifentanil, Sufentanil, Alfentanil, Carfentanil
5.4.2.7 Fentanyl Patches
5.4.2.8 Codeine
5.4.2.9 Hydrocodone and Oxycodone
5.4.2.10 Tramadol
5.4.2.11 Tapentadol
5.4.3 Partial Agonist Opioids
5.4.3.1 Buprenorphine
5.4.3.2 Simbadol
5.4.3.3 Zorbium
5.4.3.4 Sustained or Extended Release (SR or ER) Buprenorphine
5.4.3.5 Buprenorphine Patches
5.4.4 Agonist/Antagonist Opioids: Butorphanol and Nalbuphine
5.4.5 Opioid Antagonists: Naloxone, Nalmefene, Naltrexone
5.4.6 Mixing Opioids
5.5 Non-steroidal Anti-inflammatory Drugs (NSAIDs)
5.5.1 Washout
5.5.2 Piprant Class
5.6 Corticosteroids
5.7 Cannabinoids
5.8 Local Anesthetics
5.8.1 Nocita
5.8.2 Systemic Toxicity
5.8.3 Lidocaine as a CRI
5.9 Gabapeninoids
5.9.1 Gabapentin
5.9.2 Pregabalin
5.10 Alpha-2 Agonists
5.10.1 Xylazine, Medetomidine, Dexmedetomidine, Romifidine, Detomidine
5.10.2 Zenalpha® (Medetomidine and Vatinoxan)
5.11 N-Methyl-D-Aspartate (NMDA) Antagonists
5.11.1 Ketamine and Tiletamine
5.11.2 Precautions/Contraindications
5.11.3 Amantadine and Memantine
5.12 Neurokinin-1 Inhibitors
5.13 Bisphosphonates
5.14 Acetaminophen (Paracetamol)
5.15 Frunevetmab (Solensia®) and Bedinvetmab (Librela®)
5.16 Polysulfated Glycosaminoglycans (PSGAGs)
5.17 Dipyrone (Metamizole)
5.18 Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)
5.19 Acepromazine
5.20 Trazodone
References
Chapter 6 Regional Anesthesia and Local Blocks
6.1 Introduction
6.2 Current Drug Options for Regional Anesthesia and Nerve Blocks
6.2.1 Mixing Local Anesthetics
6.2.2 Adjunctive Agents
6.2.3 Volume Expansion, Onset Time, and Buffering
6.2.4 Maximum Recommended Dose (MRD)
6.2.5 Equipment Selection
6.3 Dental and Facial Regional/Local Anesthesia
6.4 Dentistry and Facial Blocking Techniques
6.4.1 Inferior (Caudal) Alveolar Nerve Block (Extraoral/Intraoral)
6.4.2 Middle Mental Foramen Nerve Block
6.4.3 Infraorbital Nerve Block
6.4.4 Major Palatine Block: Small Animal
6.4.5 Caudal Maxillary Block
6.4.6 Auriculopalpebral Nerve Block: Motor Blockade of the Eyelid
6.4.7 Retrobulbar Block
6.4.8 Frontal Nerve (Supraorbital Foramen) Block
6.4.9 Auriculotemporal Block + Greater Auricular Block
6.5 Common Regional and Local Anesthetic Techniques: Less Specified
6.5.1 Intraperitoneal Lavage Technique for Dogs and Cats
6.5.2 Incisional Line Block
6.5.3 Circumferential Block
6.6 Regional and Local Blocks of the Thorax and Abdomen
6.6.1 Intercostal Blocks
6.6.2 Interpleural Block
6.6.3 Intratesticular and Spermatic Cord Block
6.6.4 Sacrococcygeal Block
6.6.5 Epidural
6.6.6 Spinal Anesthesia
6.6.7 Epidural Catheter
6.6.8 Erector Spinae Plane Block (ESP)
6.6.9 Thoracic Paravertebral Block
6.6.10 Transverus Abdominis Plane (TAP) Block
6.7 Blocks of the Limbs
6.7.1 Femoral-Saphenous Nerve Complex Block
6.7.2 Sciatic Nerve Block
6.7.3 Brachial Plexus Block
6.7.4 Radial, Ulnar, Median, and Musculocutaneous (RUMM) Nerve Blocks
6.8 Common Equine Techniques
6.8.1 Local Analgesia for Horse Castration
6.8.2 Caudal Epidural in the Horse
6.9 Common Production Animal Techniques
6.9.1 Analgesia for Castration
6.9.2 Cornual Nerve Block
6.9.3 Analgesia for Livestock Epidural
6.9.4 Local Anesthetic Blocks for Exotics and Laboratory Animals
References
Chapter 7 Analgesia for Acute Pain
7.1 Introduction
7.2 Fear, Anxiety, and Stress in the Acute Pain Response
7.3 Multimodal Therapies
7.4 Types of Acute Pain
7.4.1 Surgical Pain
7.4.1.1 Premedication
7.4.1.2 Induction
7.4.1.3 Maintenance
7.4.1.4 Postoperative Analgesic Medications
7.4.1.5 Pain Vacation
7.4.1.6 Take-homeAnalgesics
7.5 Creating an Effective Acute Pain Analgesic Plan
7.5.1 Continuous Rate Infusions
7.6 Analgesia Plans for Painful Procedures
7.6.1 Reproductive Tract Surgery
7.6.1.1 Premedication
7.6.1.2 Regional Anesthesia
7.6.1.3 Maintenance
7.6.1.4 Postoperative Analgesic Plan
7.6.1.5 Home Medications
7.6.2 Analgesia for Surgery Involving the Eye
7.6.2.1 Premedication
7.6.2.2 Regional Anesthesia
7.6.2.3 Maintenance
7.6.2.4 Postoperative Analgesic Plan
7.6.2.5 Home Medications
7.6.3 Analgesia Techniques for Surgery Involving the Ear
7.6.3.1 Premedication
7.6.3.2 Regional Anesthesia
7.6.3.3 Maintenance
7.6.3.4 Postoperative Analgesic Plan
7.6.3.5 Home Medications
7.6.4 Gastrointestinal Procedures or Acute Abdominal Pain
7.6.4.1 Premedication
7.6.4.2 Maintenance
7.6.4.3 Regional Anesthesia
7.6.4.4 Postoperative Analgesic Plan
7.6.4.5 Home Medications
7.6.5 Thoracic Procedures
7.6.5.1 Premedication
7.6.5.2 Maintenance
7.6.5.3 Regional Anesthesia
7.6.5.4 Postoperative Analgesic Plan
7.6.5.5 Home Medications
7.6.6 Protocols for Patients with Cranial Disease, Injury, or Neurosurgery
7.6.6.1 Premedication
7.6.6.2 Maintenance
7.6.6.3 Regional Anesthesia
7.6.6.4 Postoperative Analgesic Plan
7.6.6.5 Home Medications
7.6.7 Analgesia Protocols for the Patient with Urinary Disease
7.6.7.1 Premedication
7.6.7.2 Regional Anesthesia
7.6.7.3 Maintenance
7.6.7.4 Postoperative Analgesic Plan
7.6.7.5 Home Medications
7.6.8 Minimally Invasive Procedures
7.6.8.1 Premedication
7.6.8.2 Regional Analgesia
7.6.8.3 Maintenance
7.6.8.4 Postoperative Analgesic Plan
7.6.8.5 Home Medications
7.7 Orthopedic Procedures
7.7.1 Orthopedic Procedures of the Forelimb
7.7.1.1 Premedication
7.7.1.2 Maintenance
7.7.1.3 Regional Anesthesia
7.7.1.4 Postoperative Analgesic Plan
7.7.1.5 Home Medications
7.7.2 Hindlimb Amputation, Spinal Disease, Spinal Surgery, and Pelvic Fracture Repair
7.7.2.1 Premedication
7.7.2.2 Maintenance
7.7.2.3 Regional Anesthesia
7.7.2.4 Postoperative Analgesic Plan
7.7.2.5 Home Medications
7.7.3 Surgery of the Tail
7.7.4 Mandibulectomy/Maxillectomy
7.7.4.1 Inferior Alveolar (Mandibular) Blocks
7.7.4.2 Maxillary Blocks
7.8 Postoperative Patient Evaluation
7.9 Management of Painful Dermatologic Conditions
7.9.1 Sensory Perception in the Skin
7.9.2 Recognizing Cutaneous Discomfort
7.9.3 Painful and Pruritic Cutaneous Conditions
7.9.3.1 Allergic Skin Disease
7.9.3.2 Skin Infections
7.9.3.3 Autoimmune and Immune-mediated Dermatopathies
7.9.3.4 Cutaneous Burns
7.9.4 Treatment of Cutaneous Pain and Pruritus
7.10 Conclusion
References
Chapter 8 Analgesia for the Pregnant, Neonatal, and Pediatric Patient
8.1 Introduction
8.1.1 Pain Management During Pregnancy
8.1.2 Analgesic Drugs Used During Pregnancy and C-Sections
8.1.2.1 Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
8.1.2.2 Opioids
8.1.2.3 Alpha-2Agonists
8.1.2.4 Dissociative Agents
8.1.2.5 Local and Regional Blocks
8.2 Postoperative Analgesia
8.3 Anesthesia and Analgesia Case Management for a Cesarean Section
8.4 Pain Management for Neonates and Pediatrics
8.4.1 Insulting the Neonatal Pain Pathways
8.4.1.1 NMDA Receptors
8.4.1.2 Cutaneous Receptors
8.4.2 Treatment of Pain in Neonatal and Pediatric Patients
8.4.2.1 Opioids
8.4.2.2 Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
8.4.2.3 Alpha-2Agonists
8.4.2.4 Local and Regional Blocks
References
Chapter 9 Analgesia in the Emergency and Critical Care Setting
9.1 Introduction
9.2 Treating Pain in the Emergency and Critical Care Veterinary Patient
9.3 Evaluating Pain in ER and ICU Patients
9.4 Nursing Care and the Role of Pain Management in Kirby’s Rule of 20
9.5 Pain and the Physiological Stress Response: A Summary
9.6 Sleep Deprivation
9.7 Windup Pain in the ER
9.8 Techniques and Nuances for Analgesic Delivery in the Emergency Room
9.8.1 Pain Vacations (Acute Pain)
9.8.2 Lidocaine Use in ECC
9.8.3 Opioid Analgesia for Emergency and Critical Care Patients
9.8.4 Local/Regional Analgesia in ECC
9.8.5 NSAIDS
9.8.6 Maropitant
9.8.7 Physical Rehabilitation Methods in ECC
9.9 Common Painful Conditions in the ER/ICU Setting
9.9.1 Fractures
9.9.2 Acute Soft Tissue Injuries
9.9.3 Feline Lower Urinary Tract Obstruction
9.9.4 Trauma Patients
9.9.5 Abdominal Pain in ECC Patients
9.9.6 Acute Swelling and Edema
9.10 Conclusion
References
Chapter 10 Chronic Pain Management for the Companion Animal
10.1 Introduction
10.2 The Complexity of Chronic Pain
10.3 Neuropathic Pain
10.4 Common Chronic Pain Conditions
10.4.1 Chronic Joint Pain-Osteoarthritis (OA)
10.4.2 Oncologic/Malignant Pain
10.4.3 Chiari Malformation Pain
10.4.4 Headaches and Migraines in Animals
10.4.5 Meningitis
10.4.6 Chronic Wounds
10.5 Assessing Chronic Pain
10.6 Goals and Modalities for Treating Chronic Pain
10.7 Pharmacological Interventions
10.7.1 Pain Vacation (Chronic Pain)
10.7.2 Mesotherapy
10.7.3 Transdermal Medications
10.7.4 Non-steroidal Anti-Inflammatory Drugs (NSAIDs)
10.7.5 Acetaminophen
10.7.6 Corticosteroids
10.7.7 Opioids
10.7.8 Atypical Opioids: Tramadol and Tapentadol
10.7.9 Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)
10.7.10 Gabapentinoids: Gabapentin and Pregabalin
10.7.11 N-Methyl-D-Aspartate Antagonists
10.7.12 Neurokinin-1 Inhibitors
10.7.13 Bisphosphonates
10.7.14 Anti-NGF, Monoclonal Antibodies
10.7.15 Nutraceuticals and Animal Health Supplements
10.8 Lifestyle Modifications
10.8.1 Weight Loss and Appropriate Nutrition
10.8.2 Routine Exercise and Physical Therapy
10.8.3 Thinking “Out of the Box” through Environment Modifications
10.9 Conclusion
References
Chapter 11 Analgesia for Shelter Medicine and Trap–Neuter–Return Programs
11.1 Introduction
11.2 Multimodal Analgesia
11.2.1 Opioids
11.2.2 Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
11.2.3 NMDA Antagonists
11.2.4 Alpha-2 Adrenoceptor Agonists
11.2.5 Local Anesthetics
11.2.6 Adjunct Therapies
11.3 HQHVSN and TNR Programs
11.4 Rabbits
11.5 Conclusion
References
Chapter 12 Pain Management in Equids
12.1 Introduction
12.2 Pain Assessment in Horses
12.3 Common Analgesics and Strategies in Horses
12.3.1 Butorphanol
12.3.2 Buprenorphine
12.3.3 Meperidine
12.3.4 Tramadol
12.3.5 Pure Opioid Agonists
12.3.6 Non-steroidal Anti-inflammatories
12.3.7 NMDA Receptor Antagonists
12.3.8 Alpha-2 Agonists
12.3.9 N-butylscopolammonium Bromide (NBB)
12.3.10 Dimethylsulfoxide (DMSO)
12.3.11 Prokinetics and Antispasmodics
12.3.12 Locoregional Anesthetics and Techniques
12.4 Lidocaine Use in Horses
12.4.1 Postoperative Period Lidocaine Use
12.5 Common Painful Conditions and Procedures in Horses
12.5.1 Surgical Pain
12.5.2 Gastrointestinal (Colic and Ulcers) Pain
12.5.3 Lameness
12.5.4 Osteoarthritis
12.5.5 Laminitis
12.5.6 Pleuropneumonia
12.5.7 Dystocia
12.6 Analgesia in Foals
12.7 Pain Management in the Donkey
12.7.1 Common Painful Conditions
12.7.2 Pain Scoring and Behaviors
12.7.3 Anatomic and Physiologic Distinctions from the Horse
12.7.4 Analgesics in Donkeys
12.8 Nonpharmacologic Approaches to Pain
12.9 Conclusion
References
Chapter 13 Food and Fiber Species
13.1 Introduction
13.2 Cattle
13.2.1 Bovine or Cattle Medications
13.2.1.1 Opioids
13.2.1.2 NSAIDS
13.2.1.3 Alpha-2-AdrenergicAgonists
13.2.1.4 NMDA Antagonists
13.2.2 Regional Anesthesia and Analgesia
13.2.2.1 Local Anesthetic Agents
13.2.2.2 Intravenous Regional Anesthesia
13.2.2.3 Teat Block
13.2.2.4 Infusion of the Teat Cistern
13.2.2.5 Epidural Analgesia
13.2.2.6 Analgesia for Dehorning
13.2.2.7 Spermatic Cord Block
13.2.3 Analgesic Adjuvants
13.2.3.1 Gabapentin
13.2.3.2 Continuous Infusion Analgesia
13.2.4 Withdrawal Period
13.3 Sheep (Ovine) and Goat (Caprine) Medications
13.3.1.1 Opioids
13.3.1.2 NSAIDs
13.3.1.3 Alpha-2-AdrenergicAgonists
13.3.1.4 NMDA Antagonists
13.3.2 Regional and Local Anesthesia
13.3.2.1 Cornual Block
13.3.2.2 The Inverted L-Blockor 7-Block
13.3.2.3 Paravertebral Nerve Block
13.3.2.4 Caudal Epidural
13.3.3 Intravenous Regional Anesthesia
13.3.3.1 Bier Block
13.3.3.2 Intratesticular Block
13.3.3.3 Continuous Rate Infusions
13.3.4 Pain Management for Pigs (Swine)
13.3.4.1 Opioids
13.3.4.2 NSAIDs
13.3.4.3 Alpha-2Adrenergic Agonists
13.3.4.5 Lumbosacral Epidural Block
13.3.4.6 Continuous Rate Infusions
13.4 Pain Management for Camelids
13.4.1 Camelid Medications
13.4.1.1 Opioids
13.4.1.2 NSAIDS
13.4.1.3 Alpha-2Agonists
13.4.1.4 Local Anesthetics
13.4.1.5 NMDA Antagonists
13.4.1.6 CRI Techniques
13.4.1.7 Tramadol
13.4.1.8 Gabapentin
13.5 Conclusion
Chapter 14 Exotic Companion Animals
14.1 Introduction
14.2 Why Treat Pain?
14.3 Rabbits
14.3.1 Painful Behaviors: Rabbits
14.3.2 Pain Scoring: Rabbits
14.3.3 Nursing Care and Environmental Management: Rabbits
14.3.4 Common Analgesics in Rabbits
14.4 Rodents and Ferrets
14.4.1 Mice
14.4.1.1 Pain Scoring: Mice
14.4.2 Rats and Ferrets
14.4.2.1 Pain Scoring: Rats and Ferrets
14.4.3 Gerbils
14.4.4 Hamsters
14.4.5 Guinea Pigs
14.4.5.1 Pain Scoring: Gerbils, Hamsters, Guinea Pigs, and Ferrets
14.4.5.2 Common Analgesics in Rodents
14.4.5.3 Opioids
14.4.5.4 NSAIDs
14.4.5.5 Regional and Local Anesthesia
14.5 Multimodal Analgesia: All Species
14.6 Avian Analgesia
14.6.1 Recognizing Relevant Behaviors for Each Species
14.6.2 Avian Pain Scoring and Management
14.6.3 Avian Drug Delivery
14.6.4 Common Analgesics in Birds
14.6.4.1 NSAIDS
14.6.4.2 Opioids
14.6.4.3 Regional and Local Analgesia
14.6.4.4 Adjunctive Analgesics
14.7 Reptile Analgesia
14.7.1 Causes of Pain in Reptiles
14.7.2 Analgesic Medications
14.7.2.1 Opioids
14.7.2.2 NSAIDs
14.7.2.3 Local Anesthetics
14.7.2.4 Adjunctive Analgesics in Reptiles
14.8 Analgesia in Fish and Amphibians
14.8.1 Fish and Amphibian Treatment Strategies
14.9 Analgesia in Invertebrates
14.9.1 Invertebrate Analgesia Strategies
14.10 Conclusion
References
Chapter 15 Analgesia in Zoo Animals
15.1 Veterinary Technicians in a Zoological Setting
15.1.1 Types of Questions to Ask Keepers Include
15.2 Recognizing Pain in Non-domestic Animals
15.2.1 Scoring Pain and Discomfort
15.3 Treatment
15.4 Medication Administration
15.5 Adjunctive Therapies
15.6 Choosing a Pain Regimen
15.7 Taxon-specific Considerations
15.7.1 Elephants
15.7.2 Great Apes
15.7.3 Old World and New World Non-human Primates (NHP)
15.7.4 Exotic Ungulates
15.7.5 Swine
15.7.6 Wildlife
15.8 Conclusion
References
Chapter 16 Physical Rehabilitation
16.1 Scope of Training for the Team
16.1.1 Team Approach to Care
16.1.2 Applications in Veterinary Medicine
16.2 The Veterinary Technician and Physical Rehabilitation
16.2.1 Common Conditions and Therapeutic Modalities
16.2.2 General Wound Healing
16.2.3 Bone
16.2.4 Muscle
16.2.5 Tendons and Ligaments
16.2.6 Articular Cartilage
16.3 Client Communication and Activity Modification
16.4 Patient Assessment
16.4.1 Veterinary Diagnosis – The Rehabilitation Team
16.4.2 Objective Outcomes: Goniometry and Muscle Girth
16.4.3 Pain and Disability Scoring – Methodology in Pain Scoring and Assessment
16.4.4 The Musculoskeletal System
16.4.5 Structural and Postural Evaluation
16.4.6 Gait Analysis and Movement
16.4.7 Lameness
16.4.8 The Aging Patient
16.5 Patient Management
16.5.1 Assistive Devices: Mobility Wheelchairs, Harnesses, and Footwear
16.5.2 Bracing, Splinting, and Prosthesis
16.5.3 Kinesio Taping
16.5.4 Environmental Modifications
16.6 Therapeutic Modalities and Emerging Treatments
16.6.1 Superficial Thermal Therapies
16.6.2 Photobiomodulation (Therapeutic Laser)
16.6.3 Electrical Stimulation
16.6.4 Extracorporeal Shock Wave Therapy (ESWT)
16.6.5 Therapeutic Ultrasound (ThUS)
16.6.6 Electro-Magnetic Therapy
16.7 Manual Therapy and Myofascial Trigger Points
16.7.1 Myofascial Trigger Points
16.7.2 Joint Mobilizations and Chiropractic
16.7.3 Joint Range of Motion – Passive
16.7.4 Therapeutic Massage
16.8 Emerging Therapeutic Medical Interventions
16.8.1 Regenerative Medicine and Biological Treatments
16.8.2 Corticosteroids and Hyaluronic Acid
16.8.3 Stem Cells
16.8.4 Platelet Rich Plasma (PRP)
16.8.5 Interleukin-1 Receptor Antagonist Protein (IRAP)
16.8.6 Prolotherapy
16.8.7 Emerging Technologies: Radiosynoviorthesis (Conversion Electron Therapy)
16.8.8 Emerging Technologies: Viscoelastic Therapies – Injectable Hydrogel Microparticles and Polyacrylamide Gels
16.9 Therapeutic Exercise and Aquatic Therapy
16.9.1 Therapeutic Exercise Principles and Application
16.9.2 Land Treadmills
16.9.3 Hydrotherapy or Aquatic Therapy
Appendix 16.A Obtaining Goniometric Measurements in the Canine Patient
Appendix 16.B Limb Circumference
Appendix 16.C Postural Compensations and Associated Medical Conditions
Appendix 16.D Photobiomodulation Example Protocols Adapted from (Monici et al. 2019)
Appendix 16.E Electrical Stimulation Example Protocols (Armitage 2019)
Appendix 16.F Myofascial Trigger Point (MTrP) and Myofascial Pain Syndrome (MPS) Terminology
Appendix 16.G Myofascial Trigger Point Examination Techniques
Appendix 16.H Techniques Addressing Myofascial Trigger Points
Appendix 16.I Joint Mobilizations
Appendix 16.J Passive Range of Motion
Appendix 16.K Therapeutic Massage Techniques
Appendix 16.L Therapeutic Exercises for Early Rehabilitation
Appendix 16.M Sample Guidelines
References
Chapter 17 Nutrition and Integrative Medicine
17.1 Nutrition – The 5th Vital Assessment
17.1.1 Components of a Nutrition Assessment
17.1.2 Nutrition Plan
17.1.3 Complete and Balanced Nutrition
17.1.4 Obesity’s Role in Inflammation and Pain
17.1.5 Key Nutritional Factors
17.1.6 Macronutrients and Micronutrients
17.1.7 Antioxidants
17.1.8 Nutrient-Focused Diets
17.2 Microbiota Health
17.2.1 Prebiotics
17.2.2 Probiotics
17.2.3 Fecal Microbial Transplant (FMT)
17.2.4 Postbiotics
17.3 Cannabinoid Medicine
17.3.1 History of Cannabis
17.3.2 Cannabis Potential in Veterinary Medicine
17.4 The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome)
17.4.1 Primary Cannabinoid Receptors
17.4.2 Endocannabinoids
17.4.3 Retrograde Signaling
17.4.4 Exogenous Cannabinoids
17.4.5 Major Cannabinoids
17.4.6 Minor Cannabinoids
17.4.7 Terpenoids and Flavonoids
17.4.8 Entourage Effect and Synergy
17.5 Cannabinoid Role in Pain Management
17.5.1 Acute Pain
17.5.2 Chronic Pain
17.5.3 G-Coupled Protein Receptors (GPR)
17.5.4 Glycine Receptors (GlyR)
17.5.5 N-Methyl-d-Aspartate (NMDA) Receptor
17.5.6 Peroxisome Proliferator-activated Receptors (PPAR)
17.5.7 Serotonin Receptors (5-HT)
17.5.8 Transient Receptor Potential (TRP) Cation Channel Superfamily
17.5.9 Opioids and Opioid Receptors (OPD1, OPK1, OPM1)
17.5.10 Acetaminophen and the ECS
17.5.11 Gabapentinoids
17.6 Cannabis Safety and the Veterinary Technicians Role in Client Education
17.7 Harm Reduction Education (HRE)
17.7.1 THC Intoxication
17.7.2 Cognitive Perception Modulation
17.7.3 Product Guidance
17.7.4 Dosing
17.7.5 Monitoring
17.8 Acupuncture
17.9 Supplements for Pain Management
17.9.1 Omega-3 Fatty Acids
17.9.2 Palmitoylethanolamide (PEA)
17.9.3 Turmeric (Curcumin)
17.9.4 Glucosamine/Chondroitin and Undenatured Collagen-based Supplements
17.9.5 Kratum
17.9.6 Magnesium
17.9.7 Green Lipped Mussel Extract
17.9.8 Passion Fruit Peel Extract
17.9.9 Avocado/Soybean Unsaponifiables (ASU)
17.9.10 Yucca Schidigera
17.9.11 Melatonin
17.10 Conclusion
References
Chapter 18 Pain Management for End-of-Life Care
18.1 Hospice and Palliative Care
18.1.1 Veterinary Staff in the Hospice and Palliative Care Environment
18.1.2 Work Areas
18.2 Technicians’ Roles in a Hospice and Palliative Care Practice
18.2.1 Patient Presentation and Evaluation
18.2.2 Planning of Care
18.2.3 Delivery of Care
18.2.4 Caregiver Education and Training
18.2.5 Setting Up the Physical Environment
18.2.6 Social Environment
18.2.7 Support for the Family
18.2.8 Pain Recognition and Management
18.2.8.1 Neoplasia
18.2.8.2 Osteoarthritis
18.2.8.3 Analgesia for Specific Procedures and Special Problems
18.2.9 Advocacy
18.3 Euthanasia and Analgesia for the Dying Patient
18.3.1 Euthanasia
18.3.2 Natural Death
18.3.3 Pain Management for the Dying Animal
18.4 Support for the Family of the Dying Patient
18.5 Conclusion
References
Chapter 19 Selected Case Studies in Analgesia
Index
EULA

Citation preview

本书版权归John Wiley & Sons Inc.所有

Pain Management for Veterinary Technicians and Nurses

Pain Management for Veterinary Technicians and Nurses Second Edition

Edited by

Stephen Niño Cital, RVT, SRA, RLAT, CVPP, VTS (Research Anesthesia) HHMI at Stanford University, Remedy Veterinary Specialists & Veterinary Anesthesia Nerds, LLC., CA, USA

Tasha McNerney, CVT, CVPP, VTS (Anesthesia & Analgesia)

Veterinary Anesthesia Nerds, LLC. and Mt. Laurel Animal Hospital, NJ, USA Philadelphia, PA, USA

Darci Palmer, LVT, VTS (Anesthesia & Analgesia)

Veterinary Anesthesia Nerds, LLC. and Tuskegee University College of Veterinary Medicine, AL, USA

Copyright © 2025 by John Wiley & Sons, Inc. All rights reserved, including rights for text and data mining and training of artificial technologies or similar technologies. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-­copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-­8400, fax (978) 750-­4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-­6011, fax (201) 748-­6008, or online at http://www.wiley.com/go/permission. Trademarks: Wiley and the Wiley logo are trademarks or registered trademarks of John Wiley & Sons, Inc. and/ or its affiliates in the United States and other countries and may not be used without written permission. All other trademarks are the property of their respective owners. John Wiley & Sons, Inc. is not associated with any product or vendor mentioned in this book. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-­2974, outside the United States at (317) 572-­3993 or fax (317) 572-­4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our website at www.wiley.com. Library of Congress Cataloging-­in-­Publication Data Names: Cital, Stephen Niño, editor. | McNerney, Tasha, editor. | Palmer,   Darci, editor. Title: Pain management for veterinary technicians and nurses / edited by   Stephen Niño Cital, Tasha McNerney, Darci Palmer. Description: Second edition. | Hoboken, New Jersey : Wiley-Blackwell,   [2025] | Preceded by Pain management for veterinary technicians and   nurses / editor, Mary Ellen Goldberg ; consulting editor, Nancy   Shaffran. 2015. | Includes bibliographical references and index. Identifiers: LCCN 2024023166 (print) | LCCN 2024023167 (ebook) | ISBN   9781119892380 (paperback) | ISBN 9781119892403 (adobe pdf) | ISBN   9781119892397 (epub) Subjects: MESH: Pain Management–veterinary | Pain–veterinary |   Analgesia–veterinary | Animal Technicians Classification: LCC SF910.P34 (print) | LCC SF910.P34 (ebook) | NLM SF   910.P34 | DDC 636.089/60472–dc23/eng/20240625 LC record available at https://lccn.loc.gov/2024023166 LC ebook record available at https://lccn.loc.gov/2024023167 Cover Design: Wiley Cover Image(s): © Darci Palmer, © Stephen Niño Cital, © Tasha McNerney Set in 9.5/12.5pt STIXTwoText by Straive, Pondicherry, India

v

Contents List of Contributors  xxiii Foreword  xxvii Acknowledgments  xxix About the Companion Website  xxxi 1 1.1 1.2 1.3 1.4 1.5 1.5.1 1.6 1.7 1.8 1.9 2 2.1 2.2 2.2.1 2.2.2 2.2.3 2.2.4 2.2.5 2.2.6 2.2.7 2.2.8

Advancing Veterinary Pain Management into a New Era  1 Mary Ellen Goldberg ­Introduction  1 ­Brief History of Human Pain Management  1 ­Veterinary Pain Management Through the Centuries  3 ­Animal Research Contributions  3 ­History of Animal Nursing Staff  4 National Association of Veterinary Technicians in America Recognized Veterinary Technician Specialty Academies  4 ­Eyewitness to 50 Years of Changes for Veterinary Technicians  5 ­Veterinary Technician Pioneers in Pain Management  6 ­Future Directions for Veterinary Technician Pain Management  7 ­Conclusion  7 ­References  7 Careers in Animal Pain Management  9 Tasha McNerney and Stephen Niño Cital ­Introduction  9 ­Pain Management Certifications Available for Veterinary Technicians/Nurses  9 Certified Veterinary Pain Practitioner (CVPP)  9 Veterinary Technician Specialist (Anesthesia and Analgesia), and Veterinary Technician Specialist (Laboratory Animal Medicine – Research Anesthetist)  10 Veterinary Technician Specialist (Physical Rehabilitation)  11 Surgical Research Anesthetist (SRA)  11 The University of Tennessee Companion Animal Pain Management Certificate Program  11 AAHA Pain Management Guidelines Certificate Course (AAHA Pain Management Champion)  11 WSAVA Certificate in Pain Management  12 Canine Rehabilitation Veterinary Technician Certifications  12

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2.2.9 2.2.10 2.2.11 2.2.12 2.2.13 2.2.14 2.2.15 2.2.16 2.2.17 2.3 2.4

Equine Rehabilitation Veterinary Technician Certifications  12 Certified Equine Massage Therapist  12 Animal Acupressure and Massage  12 TCVM Veterinary Technician Programs Offered by the Chi Institute  12 Animal Acupuncture  13 Low-­Stress Certifications  13 Veterinary Anaesthesia and Analgesia (MSc), (PgDip), (PgCert), or (PgProfDev)  13 Canine Arthritis Management Practitioner (CAMP)  14 Certified Companion Animal Rehabilitation Therapist (CCAT)  14 ­Leveraging Veterinary Technicians in Pain Management  14 ­Conclusion  15

3

Pain Physiology and Psychology  17 Stephen Niño Cital, Tasha McNerney, and Robin Saar ­Introduction  17 ­What Is “Pain”  17 The Negative Effects of Pain  18 ­Breaking Down the Nociceptive Pathway  18 Transduction  18 Transmission  20 Modulation  20 Perception  20 The Dorsal Horn  21 Ventral Horn and Intermediate Zone  23 White Matter  23 Descending Pathways  23 Spinothalamic Tract  23 Spinoreticular Tract  24 Peripheral Sensitization  24 Central Sensitization  24 ­The Endocannabinoid System and Pain  27 ­The Gate Control Theory  28 ­Psychological Aspects of Pain  29 Personality and the Pain Experience  29 Stress and Anxiety on Pain  29 Pain Catastrophizing  29 Boredom and Pain  30 Neuroplasticity and the Memory of Pain  31 Caregiver Placebo  31 ­Types of Pain  32 Somatic, Visceral, and Referred Pain  32 Physiological/Adaptive/Acute Pain  32 Pathological/Maladaptive/Chronic Pain  33 Neuropathic Pain  33 Radicular Pain  34 Chronic/Persistent Postsurgical Pain  34 Complex Regional Pain Syndrome  35

3.1 3.2 3.2.1 3.3 3.3.1 3.3.2 3.3.3 3.3.4 3.3.5 3.3.6 3.3.7 3.3.8 3.3.9 3.3.10 3.3.11 3.3.12 3.4 3.5 3.6 3.6.1 3.6.2 3.6.3 3.6.4 3.6.5 3.6.6 3.7 3.7.1 3.7.2 3.7.3 3.7.4 3.7.5 3.7.6 3.7.7

Contents

3.7.8 3.8 3.8.1 3.8.2 3.8.3 3.8.4 3.8.5 3.8.6 3.8.7 3.8.8 3.8.9 3.8.10

Social Resilience and Pain  35 ­The Microbiome and Pain Pathophysiology  35 What Is a Microbiome?  36 Determining “Healthy” in a Microbiome  37 Gut Microbiome Imbalance or Dysbiosis  37 The Gut-­Brain Axis  38 Microbial Derived Mediators  38 Pathogen-­Associated Molecular Patterns (PAMPs)  38 Microbial-­Derived Metabolites  39 Neurotransmitters or Neuromodulators  39 Endocannabinoid Axis  41 Pain Medication and the Microbiome  42 ­References  42

4

Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species  47 Stephen Niño Cital, Ian Kanda, Taly Reyes, Jessica Birdwell, and Mary Ellen Goldberg ­Introduction  47 ­Pain Domains  48 Pain Intensity and Affect  48 Temporal Dimensions  48 Location and Bodily Distribution of Pain  48 ­Disposition and Personality  48 ­Breed or Species Bias  50 ­Dysphoria, Emergence Agitation, and Emergence Delirium  51 ­Placebo, Caregiver Placebo, and Placebo-­by-­Proxy  52 ­Non–species-­specific Assessments  52 Quantitative Sensory Testing (QST)  52 Temporal Summation (TS)  53 Nociceptive Withdrawal Reflex (NWR)  53 Gait Analysis  53 Pain Biomarkers  53 Machine Learning and Artificial Intelligence (AI)  54 Activity Monitors (AMs)  54 Facial Expression or Grimace Scales  55 ­Clinical Pain Scoring Tools (Canine and Feline)  55 Canine Acute Pain Scoring  56 Glasgow Composite Measure Pain Scale – Short and Long Forms (CMPS) (Validated)  56 French Association for Animal Anesthesia and Analgesia Pain Scoring System (4A-­Vet) (Validated)  58 University of Melbourne Pain Scale (UMPS) (Validated)  58 Canine Chronic Pain Scoring  58 Canine Brief Pain Inventory (CBPI) (Validated)  58 Helsinki Chronic Pain Index (HCPI) (Validated)  59 Liverpool Osteoarthritis in Dogs (LOAD) (Validated)  59 Feline Acute Pain Scoring  59

4.1 4.2 4.2.1 4.2.2 4.2.3 4.3 4.4 4.5 4.6 4.7 4.7.1 4.7.2 4.7.3 4.7.4 4.7.5 4.7.6 4.7.7 4.7.8 4.8 4.8.1 4.8.1.1 4.8.1.2 4.8.1.3 4.8.2 4.8.2.1 4.8.2.2 4.8.2.3 4.8.3

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4.8.3.1 4.8.3.2 4.8.4 4.8.4.1 4.8.4.2 4.8.4.3 4.8.4.4 4.8.4.5 4.8.4.6 4.8.4.7 4.8.4.8 4.9 4.9.1 4.10 4.11 4.11.1 4.12 4.12.1 4.12.1.1 4.12.1.2 4.12.1.3 4.12.1.4 4.12.1.5 4.12.2 4.13 4.13.1 4.13.2 4.13.3 4.13.4 4.14 4.14.1 4.14.2 4.14.3 4.15 4.15.1 4.15.2 4.15.3 4.16 4.16.1 4.16.2 4.16.3 ­

Glasgow Composite Measure Pain Scale-­Short-­Form (CMPS-­SF) (Validated)  59 Feline Grimace Scale (FGS) (Validated)  60 Feline Chronic Pain Scoring  60 Client-­specific Outcome Measures – Feline (CSOMf) (Validated)  60 Montreal Instrument for Cat Arthritis Testing-­caretaker (MI-­CAT-(c)) (Validated)  60 Feline Musculoskeletal Pain Index (FMPI) (Not Validated)  60 Oral Pain Scale – Canine/Feline (COPS–C/F) (Validated)  62 Cincinnati Orthopedic Disability Index (CODI) (Not Validated)  62 HHHHHMM Scale (Not Validated)  62 VetMetrica™ Health-­related Quality of Life (HRQoL) (Validated)  62 Food and Fiber Species Pain Recognition and Scoring  63 ­Bovids  63 Indications of Pain in Cattle  71 ­Small Ruminants and Camelids  71 ­Swine  73 Normal Behavioral Observations in Swine  73 ­Equid Pain Recognition and Scoring  73 Horses  74 Appearance of the Normal Horse  74 Somatic Pain Indicators  75 Signs of Laminitis Pain Vary with the Progression of the Disease  75 Visceral Pain Indicators  75 Horse Grimace Scale  75 Donkeys  77 ­Exotic Species Pain Recognition and Scoring  77 Birds  77 Appearance of a Non-­painful Bird  78 Appearance of a Painful Bird  78 Developing a Pain Score in Birds  81 ­Reptiles  82 Appearance of a Nonpainful Reptile  82 Appearance of a Reptile in Pain  82 Developing a Pain Score in Reptiles  83 Amphibians and Fish  84 Appearance of a Nonpainful Fish and Amphibian  84 Appearance of a Painful Fish and Amphibian  84 Developing a Pain Scoring Assessments in Fish and Amphibians  84 ­Small Exotic Mammals  85 Appearance of Nonpainful Small Exotic Mammals  85 Appearance of Painful Small Exotic Mammals  85 Developing a Pain Score in Small Exotic Mammals  85 References  89

5

Analgesia Pharmacology  95 Darci Palmer and Stephen Niño Cital ­Introduction  95 ­Definitions  95

5.1 5.2

Contents

5.3 5.4 5.4.1 5.4.2 5.4.2.1 5.4.2.2 5.4.2.3 5.4.2.4 5.4.2.5 5.4.2.6 5.4.2.7 5.4.2.8 5.4.2.9 5.4.2.10 5.4.2.11 5.4.3 5.4.3.1 5.4.3.2 5.4.3.3 5.4.3.4 5.4.3.5 5.4.4 5.4.5 5.4.6 5.5 5.5.1 5.5.2 5.6 5.7 5.8 5.8.1 5.8.2 5.8.3 5.9 5.9.1 5.9.2 5.10 5.10.1 5.10.2 5.11 5.11.1 5.11.2 5.11.3 5.12 5.13 5.14 5.15 5.16

­ nalgesic Drugs  96 A ­Opioids  97 Full Opioid Agonists  97 Individual Drug Facts  99 Morphine  99 Meperidine (Pethidine)  99 Methadone  99 Hydromorphone  100 Oxymorphone  100 Fentanyl, Remifentanil, Sufentanil, Alfentanil, Carfentanil  100 Fentanyl Patches  100 Codeine  101 Hydrocodone and Oxycodone  101 Tramadol  101 Tapentadol  102 Partial Agonist Opioids  102 Buprenorphine  102 Simbadol  104 Zorbium  104 Sustained or Extended Release (SR or ER) Buprenorphine  104 Buprenorphine Patches  105 Agonist/Antagonist Opiods: Butorphanol and Nalbuphine  105 Opioid Antagonists: Naloxone, Nalmefene, Naltrexone  105 Mixing Opioids  106 ­Non-­steroidal Anti-­inflammatory Drugs (NSAIDs)  106 Washout  108 Piprant Class  108 ­Corticosteroids  109 ­Cannabinoids  109 ­Local Anesthetics  110 Nocita  110 Systemic Toxicity  110 Lidocaine as a CRI  111 ­Gabapeninoids  111 Gabapentin  111 Pregabalin  112 ­Alpha-­2 Agonists  112 Xylazine, Medetomidine, Dexmedetomidine, Romifidine, Detomidine  112 Zenalpha® (Medetomidine and Vatinoxan)  113 ­N-­Methyl-­D-­Aspartate (NMDA) Antagonists  114 Ketamine and Tiletamine  114 Precautions/Contraindications  115 Amantadine and Memantine  115 ­Neurokinin-­1 Inhibitors  115 ­Bisphosphonates  116 ­Acetaminophen (Paracetamol)  116 ­Frunevetmab (Solensia®) and Bedinvetmab (Librela®)  117 ­Polysulfated Glycosaminoglycans (PSGAGs)  117

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5.17 5.18 5.19 5.20 6 6.1 6.2 6.2.1 6.2.2 6.2.3 6.2.4 6.2.5 6.3 6.4 6.4.1 6.4.2 6.4.3 6.4.4 6.4.5 6.4.6 6.4.7 6.4.8 6.4.9 6.5 6.5.1 6.5.2 6.5.3 6.6 6.6.1 6.6.2 6.6.3 6.6.4 6.6.5 6.6.6 6.6.7 6.6.8 6.6.9 6.6.10 6.7 6.7.1 6.7.2 6.7.3 6.7.4

­ ipyrone (Metamizole)  117 D ­Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–­Norepinephrine Reuptake Inhibitors (SNRIs)  118 ­Acepromazine  119 ­Trazodone  119 ­References  119 Regional Anesthesia and Local Blocks  127 Imeldo Laurel, Jeanette M. Eliason, Amy Dowling, Tasha McNerney, and Stephen Niño Cital ­Introduction  127 ­Current Drug Options for Regional Anesthesia and Nerve Blocks  128 Mixing Local Anesthetics  129 Adjunctive Agents  129 Volume Expansion, Onset Time, and Buffering  129 Maximum Recommended Dose (MRD)  130 Equipment Selection  131 ­Dental and Facial Regional/Local Anesthesia  133 ­Dentistry and Facial Blocking Techniques  133 Inferior (Caudal) Alveolar Nerve Block (Extraoral/Intraoral)  133 Middle Mental Foramen Nerve Block  135 Infraorbital Nerve Block  136 Major Palatine Block: Small Animal  137 Caudal Maxillary Block  138 Auriculopalpebral Nerve Block: Motor Blockade of the Eyelid  138 Retrobulbar Block  140 Frontal Nerve (Supraorbital Foramen) Block  140 Auriculotemporal Block + Greater Auricular Block  142 ­Common Regional and Local Anesthetic Techniques: Less Specified  143 Intraperitoneal Lavage Technique for Dogs and Cats  143 Incisional Line Block  143 Circumferential Block  144 ­Regional and Local Blocks of the Thorax and Abdomen  144 Intercostal Blocks  144 Interpleural Block  146 Intratesticular and Spermatic Cord Block  147 Sacrococcygeal Block  147 Epidural  149 Spinal Anesthesia  153 Epidural Catheter  153 Erector Spinae Plane Block (ESP)  156 Thoracic Paravertebral Block  157 Transverus Abdominis Plane (TAP) Block  158 ­Blocks of the Limbs  160 Femoral-­Saphenous Nerve Complex Block  160 Sciatic Nerve Block  162 Brachial Plexus Block  164 Radial, Ulnar, Median, and Musculocutaneous (RUMM) Nerve Blocks  166

Contents

6.8 6.8.1 6.8.2 6.9 6.9.1 6.9.2 6.9.3 6.9.4

­ ommon Equine Techniques  167 C Local Analgesia for Horse Castration  167 Caudal Epidural in the Horse  167 ­Common Production Animal Techniques  168 Analgesia for Castration  168 Cornual Nerve Block  170 Analgesia for Livestock Epidural  171 Local Anesthetic Blocks for Exotics and Laboratory Animals  174 ­References  175

7

Analgesia for Acute Pain  179 Tasha McNerney, Melissa Streicher, and Karen Maloa Roach ­Introduction  179 ­Fear, Anxiety, and Stress in the Acute Pain Response  180 ­Multimodal Therapies  180 ­Types of Acute Pain  181 Surgical Pain  181 Premedication  182 Induction  183 Maintenance  183 Postoperative Analgesic Medications  183 Pain Vacation  184 Take-­home Analgesics  184 Local Anesthesia Techniques  185 ­Creating an Effective Acute Pain Analgesic Plan  185 Continuous Rate Infusions  185 ­Analgesia Plans for Painful Procedures  186 Reproductive Tract Surgery  186 Premedication  187 Regional Anesthesia  187 Maintenance  187 Postoperative Analgesic Plan  187 Home Medications  187 Analgesia for Surgery Involving the Eye  188 Premedication  188 Regional Anesthesia  188 Maintenance  188 Postoperative Analgesic Plan  188 Home Medications  188 Analgesia Techniques for Surgery Involving the Ear  189 Premedication  189 Regional Anesthesia  189 Maintenance  189 Postoperative Analgesic Plan  189 Home Medications  189 Gastrointestinal Procedures or Acute Abdominal Pain  190 Premedication  190

7.1 7.2 7.3 7.4 7.4.1 7.4.1.1 7.4.1.2 7.4.1.3 7.4.1.4 7.4.1.5 7.4.1.6 7.4.1.7 7.5 7.5.1 7.6 7.6.1 7.6.1.1 7.6.1.2 7.6.1.3 7.6.1.4 7.6.1.5 7.6.2 7.6.2.1 7.6.2.2 7.6.2.3 7.6.2.4 7.6.2.5 7.6.3 7.6.3.1 7.6.3.2 7.6.3.3 7.6.3.4 7.6.3.5 7.6.4 7.6.4.1

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7.6.4.2 7.6.4.3 7.6.4.4 7.6.4.5 7.6.5 7.6.5.1 7.6.5.2 7.6.5.3 7.6.5.4 7.6.5.5 7.6.6 7.6.6.1 7.6.6.2 7.6.6.3 7.6.6.4 7.6.6.5 7.6.7 7.6.7.1 7.6.7.2 7.6.7.3 7.6.7.4 7.6.7.5 7.6.8 7.6.8.1 7.6.8.2 7.6.8.3 7.6.8.4 7.6.8.5 7.7 7.7.1 7.7.1.1 7.7.1.2 7.7.1.3 7.7.1.4 7.7.1.5 7.7.2 7.7.2.1 7.7.2.2 7.7.2.3 7.7.2.4 7.7.2.5 7.7.3 7.7.4 7.7.4.1 7.7.4.2 7.8 7.9

Maintenance  190 Regional Anesthesia  190 Postoperative Analgesic Plan  191 Home Medications  191 Thoracic Procedures  191 Premedication  191 Maintenance  192 Regional Anesthesia  192 Postoperative Analgesic Plan  192 Home Medications  192 Protocols for Patients with Cranial Disease, Injury, or Neurosurgery  193 Premedication  194 Maintenance  194 Regional Anesthesia  194 Postoperative Analgesic Plan  194 Home Medications  194 Analgesia Protocols for the Patient with Urinary Disease  194 Premedication  194 Regional Anesthesia  195 Maintenance  195 Postoperative Analgesic Plan  195 Home Medications  195 Minimally Invasive Procedures  195 Premedication  195 Regional Analgesia  196 Maintenance  196 Postoperative Analgesic Plan  196 Home Medications  196 ­Orthopedic Procedures  196 Orthopedic Procedures of the Forelimb  196 Premedication  196 Maintenance  196 Regional Anesthesia  196 Postoperative Analgesic Plan  197 Home Medications  197 Hindlimb Amputation, Spinal Disease, Spinal Surgery, and Pelvic Fracture Repair  197 Premedication  198 Maintenance  198 Regional Anesthesia  198 Postoperative Analgesic Plan  198 Home Medications  198 Surgery of the Tail  198 Mandibulectomy/Maxillectomy  200 Inferior Alveolar (Mandibular) Blocks  200 Maxillary Blocks  200 ­Postoperative Patient Evaluation  201 ­Management of Painful Dermatologic Conditions  201

Contents

7.9.1 7.9.2 7.9.3 7.9.3.1 7.9.3.2 7.9.3.3 7.9.3.4 7.9.4 7.10

Sensory Perception in the Skin  202 Recognizing Cutaneous Discomfort  202 Painful and Pruritic Cutaneous Conditions  203 Allergic Skin Disease  204 Skin Infections  204 Autoimmune and Immune-­mediated Dermatopathies  206 Cutaneous Burns  207 Treatment of Cutaneous Pain and Pruritus  211 ­Conclusion  212 ­References  212

8

Analgesia for the Pregnant, Neonatal, and Pediatric Patient  217 Darci Palmer and Natalie Pedraja ­Introduction  217 Pain Management During Pregnancy  217 Analgesic Drugs Used During Pregnancy and C-­Sections  218 Nonsteroidal Anti-­inflammatory Drugs (NSAIDs)  219 Opioids  219 Alpha-­2 Agonists  221 Dissociative Agents  222 Local and Regional Blocks  222 ­Postoperative Analgesia  224 ­Anesthesia and Analgesia Case Management for a Cesarean Section  224 ­Pain Management for Neonates and Pediatrics  227 Insulting the Neonatal Pain Pathways  227 NMDA Receptors  228 Cutaneous Receptors  228 Treatment of Pain in Neonatal and Pediatric Patients  228 Opioids  228 Nonsteroidal Anti-­inflammatory Drugs (NSAIDs)  229 Alpha-­2 Agonists  229 Local and Regional Blocks  229 ­References  229

8.1 8.1.1 8.1.2 8.1.2.1 8.1.2.2 8.1.2.3 8.1.2.4 8.1.2.5 8.2 8.3 8.4 8.4.1 8.4.1.1 8.4.1.2 8.4.2 8.4.2.1 8.4.2.2 8.4.2.3 8.4.2.4 9 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.8.1 9.8.2 9.8.3

Analgesia in the Emergency and Critical Care Setting  233 Heather Ann Scott and Rachel Stauffer ­Introduction  233 ­Treating Pain in the Emergency and Critical Care Veterinary Patient  233 ­Evaluating Pain in ER and ICU Patients  234 ­Nursing Care and the Role of Pain Management in Kirby’s Rule of 20  239 ­Pain and the Physiological Stress Response: A Summary  240 ­Sleep Deprivation  241 ­Windup Pain in the ER  242 ­Techniques and Nuances for Analgesic Delivery in the Emergency Room  242 Pain Vacations (Acute Pain)  243 Lidocaine Use in ECC  243 Opioid Analgesia for Emergency and Critical Care Patients  244

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9.8.4 9.8.5 9.8.6 9.8.7 9.9 9.9.1 9.9.2 9.9.3 9.9.4 9.9.5 9.9.6 9.10

Local/Regional Analgesia in ECC  244 NSAIDS  245 Maropitant  245 Physical Rehabilitation Methods in ECC  245 ­Common Painful Conditions in the ER/ICU Setting  246 Fractures  246 Acute Soft Tissue Injuries  247 Feline Lower Urinary Tract Obstruction  247 Trauma Patients  247 Abdominal Pain in ECC Patients  247 Acute Swelling and Edema  248 ­Conclusion  248 ­References  249

10

Chronic Pain Management for the Companion Animal  253 Taly Reyes, Jessica Birdwell, and Stephen Niño Cital ­Introduction  253 ­The Complexity of Chronic Pain  253 ­Neuropathic Pain  255 ­Common Chronic Pain Conditions  255 Chronic Joint Pain-­Osteoarthritis (OA)  255 Oncologic/Malignant Pain  257 Chiari Malformation Pain  257 Headaches and Migraines in Animals  259 Meningitis  259 Chronic Wounds  260 ­Assessing Chronic Pain  261 ­Goals and Modalities for Treating Chronic Pain  261 ­Pharmacological Interventions  261 Pain Vacation (Chronic Pain)  262 Mesotherapy  262 Transdermal Medications  263 Non-­steroidal Anti-­Inflammatory Drugs (NSAIDs)  264 Acetaminophen  265 Corticosteroids  265 Opioids  266 Atypical Opioids: Tramadol and Tapentadol  266 Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)  267 Gabapentinoids: Gabapentin and Pregabalin  268 N-­Methyl-­D-­Aspartate Antagonists  269 Neurokinin-­1 Inhibitors  269 Bisphosphonates  270 Anti-­NGF, Monoclonal Antibodies  270 Nutraceuticals and Animal Health Supplements  270 ­Lifestyle Modifications  271 Weight Loss and Appropriate Nutrition  271

10.1 10.2 10.3 10.4 10.4.1 10.4.2 10.4.3 10.4.4 10.4.5 10.4.6 10.5 10.6 10.7 10.7.1 10.7.2 10.7.3 10.7.4 10.7.5 10.7.6 10.7.7 10.7.8 10.7.9 10.7.10 10.7.11 10.7.12 10.7.13 10.7.14 10.7.15 10.8 10.8.1

Contents

10.8.2 10.8.3 10.9

Routine Exercise and Physical Therapy  271 Thinking “Out of the Box” through Environment Modifications  271 ­Conclusion  271 ­References  272

11

Analgesia for Shelter Medicine and Trap–Neuter–Return Programs  277 Anne Marie McPartlin and Erin Spencer ­Introduction  277 ­Multimodal Analgesia  277 Opioids  279 Nonsteroidal Anti-­inflammatory Drugs (NSAIDs)  279 NMDA Antagonists  281 Alpha-­2 Adrenoceptor Agonists  282 Local Anesthetics  282 Adjunct Therapies  283 ­HQHVSN and TNR Programs  283 ­Rabbits  285 ­Conclusion  286 ­References  286

11.1 11.2 11.2.1 11.2.2 11.2.3 11.2.4 11.2.5 11.2.6 11.3 11.4 11.5

Pain Management in Equids  289 Molly Cripe Birt, Rebecca Johnston, Rachael Hall, and Janel Holden 12.1 ­Introduction  289 12.2 ­Pain Assessment in Horses  289 12.3 ­Common Analgesics and Strategies in Horses  289 12.3.1 Butorphanol  290 12.3.2 Buprenorphine  291 12.3.3 Meperidine  291 12.3.4 Tramadol  291 12.3.5 Pure Opioid Agonists  291 12.3.6 Non-­steroidal Anti-­inflammatories  292 12.3.7 NMDA Receptor Antagonists  293 12.3.8 Alpha-­2 Agonists  293 12.3.9 N-­butylscopolammonium Bromide (NBB)  294 12.3.10 Dimethylsulfoxide (DMSO)  294 12.3.11 Prokinetics and Antispasmodics  294 12.3.12 Locoregional Anesthetics and Techniques  294 12.4 ­Lidocaine Use in Horses  295 12.4.1 Postoperative Period Lidocaine Use  295 12.5 ­Common Painful Conditions and Procedures in Horses  296 12.5.1 Surgical Pain  296 12.5.2 Gastrointestinal (Colic and Ulcers) Pain  296 12.5.3 Lameness  297 12.5.3.1 Acute Lameness  297 12.5.3.2 Chronic Lameness  298 12.5.4 Osteoarthritis  298 12.5.5 Laminitis  299 12

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12.5.6 12.5.7 12.6 12.7 12.7.1 12.7.2 12.7.3 12.7.4 12.7.4.1 12.7.4.2 12.7.4.3 12.7.4.4 12.8 12.9

Pleuropneumonia  300 Dystocia  301 ­Analgesia in Foals  302 ­Pain Management in the Donkey  304 Common Painful Conditions  304 Pain Scoring and Behaviors  304 Anatomic and Physiologic Distinctions from the Horse  306 Analgesics in Donkeys  306 Nonsteroidal Anti-­inflammatory Agents  306 Alpha-­2 Adrenoceptor Agonists  307 Opioids  307 Local Anesthesia/Analgesia Methods  307 ­Nonpharmacologic Approaches to Pain  308 ­Conclusion  308 ­References  308

13

Food and Fiber Species  315 Janel Holden, Rachael Hall, MegAnn Harrington, and Mary Ellen Goldberg ­Introduction  315 ­Cattle  318 Bovine or Cattle Medications  318 Opioids  318 NSAIDS  318 Alpha-­2-­Adrenergic Agonists  319 NMDA Antagonists  319 Regional Anesthesia and Analgesia  319 Local Anesthetic Agents  319 Intravenous Regional Anesthesia  320 Teat Block  321 Infusion of the Teat Cistern  321 Epidural Analgesia  321 Analgesia for Dehorning  322 Spermatic Cord Block  322 Analgesic Adjuvants  322 Gabapentin  322 Continuous Infusion Analgesia  322 Withdrawal Period  324 ­Sheep (Ovine) and Goat (Caprine) Medications  326 Opioids  326 NSAIDs  327 Alpha-­2-­Adrenergic Agonists  327 NMDA Antagonists  327 Regional and Local Anesthesia  327 Cornual Block  327 The Inverted L-­Block or 7-­Block  328 Paravertebral Nerve Block  328 Caudal Epidural  329

13.1 13.2 13.2.1 13.2.1.1 13.2.1.2 13.2.1.3 13.2.1.4 13.2.2 13.2.2.1 13.2.2.2 13.2.2.3 13.2.2.4 13.2.2.5 13.2.2.6 13.2.2.7 13.2.3 13.2.3.1 13.2.3.2 13.2.4 13.3 13.3.1.1 13.3.1.2 13.3.1.3 13.3.1.4 13.3.2 13.3.2.1 13.3.2.2 13.3.2.3 13.3.2.4

Contents

13.3.3 13.3.3.1 13.3.3.2 13.3.3.3 13.3.4 13.3.4.1 13.3.4.2 13.3.4.3 13.3.4.4 13.3.4.5 13.3.4.6 13.4 13.4.1 13.4.1.1 13.4.1.2 13.4.1.3 13.4.1.4 13.4.1.5 13.4.1.6 13.4.1.7 13.4.1.8 13.5

Intravenous Regional Anesthesia  329 Bier Block  329 Intratesticular Block  330 Continuous Rate Infusions  330 Pain Management for Pigs (Swine)  330 Opioids  332 NSAIDs  332 Alpha-­2 Adrenergic Agonists  334 NMDA Antagonists  334 Lumbosacral Epidural Block  334 Continuous Rate Infusions  335 ­Pain Management for Camelids  335 Camelid Medications  337 Opioids  337 NSAIDS  338 Alpha-­2 Agonists  339 Local Anesthetics  339 NMDA Antagonists  340 CRI Techniques  340 Tramadol  342 Gabapentin  342 ­Conclusion  342 References  342

14

Exotic Companion Animals  347 Katrina Lafferty, Elizabeth Vetrano, Mary Ellen Goldberg, and Stephen Niño Cital ­Introduction  347 ­Why Treat Pain?  348 ­Rabbits  349 Painful Behaviors: Rabbits  349 Pain Scoring: Rabbits  350 Nursing Care and Environmental Management: Rabbits  350 Common Analgesics in Rabbits  351 Opioids  352 NSAIDs  352 Regional and Local Anesthesia  352 Continuous Rate Infusions  353 ­Rodents and Ferrets  353 Mice  354 Pain Scoring: Mice  354 Rats and Ferrets  355 Pain Scoring: Rats and Ferrets  355 Gerbils  355 Hamsters  355 Guinea Pigs  356 Pain Scoring: Gerbils, Hamsters, Guinea Pigs, and Ferrets  356 Common Analgesics in Rodents  356

14.1 14.2 14.3 14.3.1 14.3.2 14.3.3 14.3.4 14.3.4.1 14.3.4.2 14.3.4.3 14.3.4.4 14.4 14.4.1 14.4.1.1 14.4.2 14.4.2.1 14.4.3 14.4.4 14.4.5 14.4.5.1 14.4.5.2

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14.4.5.3 14.4.5.4 14.4.5.5 14.5 14.6 14.6.1 14.6.2 14.6.3 14.6.4 14.6.4.1 14.6.4.2 14.6.4.3 14.6.4.4 14.7 14.7.1 14.7.2 14.7.2.1 14.7.2.2 14.7.2.3 14.7.2.4 14.8 14.8.1 14.9 14.9.1 14.10

Opioids  356 NSAIDs  358 Regional and Local Anesthesia  358 ­Multimodal Analgesia: All Species  359 ­Avian Analgesia  359 Recognizing Relevant Behaviors for Each Species  360 Avian Pain Scoring and Management  361 Avian Drug Delivery  362 Common Analgesics in Birds  365 NSAIDS  365 Opioids  365 Regional and Local Analgesia  366 Adjunctive Analgesics  366 ­Reptile Analgesia  367 Causes of Pain in Reptiles  368 Analgesic Medications  368 Opioids  369 NSAIDs  369 Local Anesthetics  369 Adjunctive Analgesics in Reptiles  371 ­Analgesia in Fish and Amphibians  371 Fish and Amphibian Treatment Strategies  372 ­Analgesia in Invertebrates  372 Invertebrate Analgesia Strategies  375 ­Conclusion  375 ­References  375

15

Analgesia in Zoo Animals  381 Lindsay Wesselmann, Mark Romanoski, Alison Mott, and Margot Monti ­Veterinary Technicians in a Zoological Setting  381 Types of Questions to Ask Keepers Include  381 ­Recognizing Pain in Non-­domestic Animals  382 Scoring Pain and Discomfort  384 ­Treatment  385 ­Medication Administration  385 ­Adjunctive Therapies  388 ­Choosing a Pain Regimen  389 ­Taxon-­specific Considerations  389 Elephants  389 Pain Interpretation  394 Treatment  395 Great Apes  398 Old World and New World Non-­human Primates (NHP)  399 Signs of Pain or Distress in Nonhuman Primates  401 Local and Regional Anesthetics  401 Exotic Ungulates  402 Nonruminant Ungulates  403 Ruminant Ungulates  404

15.1 15.1.1 15.2 15.2.1 15.3 15.4 15.5 15.6 15.7 15.7.1 15.7.1.1 15.7.1.2 15.7.2 15.7.3 15.7.3.1 15.7.3.2 15.7.4 15.7.4.1 15.7.4.2

Contents

15.7.5 15.7.6 15.8

Swine  405 Wildlife  406 ­Conclusion  407 ­References  407

16

Physical Rehabilitation  411 Kristen Hagler, Wendy Davies, and Lis Conarton ­Scope of Training for the Team  411 Team Approach to Care  413 Applications in Veterinary Medicine  413 ­The Veterinary Technician and Physical Rehabilitation  413 Common Conditions and Therapeutic Modalities  413 General Wound Healing  415 Bone  415 Muscle  415 Tendons and Ligaments  416 Articular Cartilage  417 ­Client Communication and Activity Modification  417 ­Patient Assessment  418 Veterinary Diagnosis – The Rehabilitation Team  418 Objective Outcomes: Goniometry and Muscle Girth  419 Pain and Disability Scoring – Methodology in Pain Scoring and Assessment  420 The Musculoskeletal System  422 Structural and Postural Evaluation  424 Gait Analysis and Movement  425 Lameness  425 The Aging Patient  427 ­Patient Management  427 Assistive Devices: Mobility Wheelchairs, Harnesses, and Footwear  427 Bracing, Splinting, and Prosthesis  429 Kinesio Taping  430 Environmental Modifications  430 ­Therapeutic Modalities and Emerging Treatments  431 Superficial Thermal Therapies  431 Photobiomodulation (Therapeutic Laser)  433 Electrical Stimulation  434 Extracorporeal Shock Wave Therapy (ESWT)  435 Therapeutic Ultrasound (ThUS)  435 Electro-­Magnetic Therapy  436 ­Manual Therapy and Myofascial Trigger Points  436 Myofascial Trigger Points  436 Joint Mobilizations and Chiropractic  437 Joint Range of Motion – Passive  438 Therapeutic Massage  438 ­Emerging Therapeutic Medical Interventions  439 Regenerative Medicine and Biological Treatments  439 Corticosteroids and Hyaluronic Acid  440 Stem Cells  440

16.1 16.1.1 16.1.2 16.2 16.2.1 16.2.2 16.2.3 16.2.4 16.2.5 16.2.6 16.3 16.4 16.4.1 16.4.2 16.4.3 16.4.4 16.4.5 16.4.6 16.4.7 16.4.8 16.5 16.5.1 16.5.2 16.5.3 16.5.4 16.6 16.6.1 16.6.2 16.6.3 16.6.4 16.6.5 16.6.6 16.7 16.7.1 16.7.2 16.7.3 16.7.4 16.8 16.8.1 16.8.2 16.8.3

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16.8.4 16.8.5 16.8.6 16.8.7 16.8.8



Platelet Rich Plasma (PRP)  440 Interleukin-­1 Receptor Antagonist Protein (IRAP)  440 Prolotherapy  441 Emerging Technologies: Radiosynoviorthesis (Conversion Electron Therapy)  441 Emerging Technologies: Viscoelastic Therapies – Injectable Hydrogel Microparticles and Polyacrylamide Gels  441 ­Therapeutic Exercise and Aquatic Therapy  442 Therapeutic Exercise Principles and Application  442 Land Treadmills  443 Hydrotherapy or Aquatic Therapy  444 Appendix 16.A Obtaining Goniometric Measurements in the Canine Patient  446 Appendix 16.B Limb Circumference  447 Appendix 16.C Postural Compensations and Associated Medical Conditions  447 Appendix 16.D Photobiomodulation Example Protocols Adapted from (Monici et al. 2019)  448 Appendix 16.E Electrical Stimulation Example Protocols (Armitage 2019)  448 Appendix 16.F Myofascial Trigger Point (MTrP) and Myofascial Pain Syndrome (MPS) Terminology  449 Appendix 16.G Myofascial Trigger Point Examination Techniques  449 Appendix 16.H Techniques Addressing Myofascial Trigger Points  450 Appendix 16.I Joint Mobilizations  450 Appendix 16.J Passive Range of Motion  451 Appendix 16.K Therapeutic Massage Techniques  452 Appendix 16.L Therapeutic Exercises for Early Rehabilitation  453 Appendix 16.M Sample Guidelines  454 ­References  459

17 17.1 17.1.1 17.1.1.1 17.1.1.2 17.1.1.3 17.1.2 17.1.3 17.1.4 17.1.5 17.1.6 17.1.7 17.1.8 17.2 17.2.1 17.2.2 17.2.3 17.2.4

Nutrition and Integrative Medicine  465 Robin Saar, Jaime Brassard, and Stephen Niño Cital ­Nutrition – The 5th Vital Assessment  465 Components of a Nutrition Assessment  466 Pet-­Related Components  466 Diet-­Related Components  466 Feeding Management  466 Nutrition Plan  467 Complete and Balanced Nutrition  467 Obesity’s Role in Inflammation and Pain  468 Key Nutritional Factors  468 Macronutrients and Micronutrients  470 Antioxidants  471 Nutrient-­Focused Diets  471 ­Microbiota Health  471 Prebiotics  471 Probiotics  471 Fecal Microbial Transplant (FMT)  472 Postbiotics  472

16.9 16.9.1 16.9.2 16.9.3

Contents

17.3 17.3.1 17.3.2 17.4 17.4.1 17.4.2 17.4.3 17.4.4 17.4.5 17.4.6 17.4.7 17.4.8 17.5 17.5.1 17.5.2 17.5.3 17.5.4 17.5.5 17.5.6 17.5.7 17.5.8 17.5.9 17.5.10 17.5.11 17.6 17.7 17.7.1 17.7.2 17.7.3 17.7.4 17.7.5 17.8 17.9 17.9.1 17.9.2 17.9.3 17.9.4 17.9.5 17.9.6 17.9.7 17.9.8 17.9.9 17.9.10 17.9.11 17.10

­ annabinoid Medicine  473 C History of Cannabis  473 Cannabis Potential in Veterinary Medicine  474 ­The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome)  475 Primary Cannabinoid Receptors  475 Endocannabinoids  476 Retrograde Signaling  477 Exogenous Cannabinoids  477 Major Cannabinoids  478 Minor Cannabinoids  478 Terpenoids and Flavonoids  479 Entourage Effect and Synergy  480 ­Cannabinoid Role in Pain Management  480 Acute Pain  480 Chronic Pain  481 G-­Coupled Protein Receptors (GPR)  481 Glycine Receptors (GlyR)  481 N-­Methyl-­d-­Aspartate (NMDA) Receptor  481 Peroxisome Proliferator-­activated Receptors (PPAR)  482 Serotonin Receptors (5-­HT)  482 Transient Receptor Potential (TRP) Cation Channel Superfamily  482 Opioids and Opioid Receptors (OPD1, OPK1, OPM1)  482 Acetaminophen and the ECS  483 Gabapentinoids  483 ­Cannabis Safety and the Veterinary Technicians Role in Client Education  483 ­Harm Reduction Education (HRE)  485 THC Intoxication  485 Cognitive Perception Modulation  486 Product Guidance  486 Dosing  487 Monitoring  488 ­Acupuncture  488 ­Supplements for Pain Management  489 Omega-­3 Fatty Acids  489 Palmitoylethanolamide (PEA)  490 Turmeric (Curcumin)  490 Glucosamine/Chondroitin and Undenatured Collagen-­based Supplements  491 Kratum  491 Magnesium  491 Green Lipped Mussel Extract  492 Passion Fruit Peel Extract  492 Avocado/Soybean Unsaponifiables (ASU)  492 Yucca Schidigera  493 Melatonin  493 ­Conclusion  493 ­References  494

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18 18.1 18.1.1 18.1.2 18.2 18.2.1 18.2.2 18.2.3 18.2.4 18.2.5 18.2.6 18.2.7 18.2.8 18.2.8.1 18.2.8.2 18.2.8.3 18.2.9 18.3 18.3.1 18.3.2 18.3.3 18.4 18.5

Pain Management for End-­of-­Life Care  507 Brooke Quesnell and Danielle DeCormier ­Hospice and Palliative Care  507 Veterinary Staff in the Hospice and Palliative Care Environment  508 Work Areas  508 ­Technicians’ Roles in a Hospice and Palliative Care Practice  509 Patient Presentation and Evaluation  509 Planning of Care  509 Delivery of Care  509 Caregiver Education and Training  510 Setting Up the Physical Environment  510 Social Environment  510 Support for the Family  510 Pain Recognition and Management  511 Neoplasia  511 Osteoarthritis  511 Analgesia for Specific Procedures and Special Problems  511 Advocacy  512 ­Euthanasia and Analgesia for the Dying Patient  512 Euthanasia  513 Natural Death  514 Pain Management for the Dying Animal  514 ­Support for the Family of the Dying Patient  515 ­Conclusion  515 ­References  516

19

Selected Case Studies in Analgesia  517 Tasha McNerney, Darci Palmer, and Stephen Niño Cital



Index  529

xxiii

List of Contributors Jaime Brassard, RVT, CVPP, VTS (Anesthesia & Analgesia) Founding Member and Technical Director Canadian Association of Veterinary Cannabinoid Medicine (CAVCM) Whitehorse, Yukon Territory, CA

Amy Dowling, CVT, VTS (Anesthesia & Analgesia) Assistant Anesthesia Supervisor University of Pennsylvania Veterinary Hospital Philadelphia, PA, USA

Lis Conarton, MSW, LVT, CCRP, CVPP, VTS (Physical Rehabilitation) Director of Organizational Culture and Engagement & CARE Pet Therapy Manager and Veterinary Rehabilitation Provider Veterinary Medical Center of CNY East Syracuse, NY, USA

Jeanette M. Eliason, CVT, RDH, VTS (Dentistry) Veterinary Nurse Supervisor and Staff Dental Hygienist in the Dentistry & Oral Surgery Service, Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania Philadelphia, PA, USA

Molly Cripe Birt, RVT, VTS (Equine Veterinary Nursing) Senior Large Animal Surgery Technologist Purdue University College of Veterinary Medicine West Lafayette, IN, USA Wendy Davies, CVT, CCRVT, VTS (Physical Rehabilitation) Veterinary Rehabilitation Technician, College of Veterinary Medicine University of Florida Gainesville, FL, USA Danielle DeCormier, LVT, VTS (Oncology) Director of Clinical Services Education MedVet Whitmore Lake, MI, USA

Mary Ellen Goldberg, LVT, CVT, SRA, CCRVT, CVPP, VTS (Lab Animal Medicine-­ Retired), VTS (Physical Rehabilitation-­ Retired), VTS (Anesthesia & Analgesia-­Honorary) IACUC Member, Mannheimer Foundation Inc. & Independent Contractor Boynton Beach, FL, USA Kristen Hagler, RVT, CCRP, CVPP, VTS (Physical Rehabilitation) Head of Canine Physical Rehabilitation Services, Circle Oak Ranch Equine and Canine Rehabilitation Petaluma, CA, USA

xxiv

List of Contributors

Rachael Hall, LVT Veterinary Student, Class of 2027, formerly ECC & Anesthesia Veterinary Technician Washington State University College of Veterinary Medicine Pullman, WA, USA MegAnn Harrington, CVT, VTS (Production Animal Internal Medicine) Veterinary Technician Specialist Nashville Animal Hospital Livestock Consulting Services Nashville, AR, USA Janel Holden, LVT, VTS (Anesthesia & Analgesia) Veterinary Technician Specialist, Washington State University College of Veterinary Medicine Pullman, WA, USA Rebecca Johnston, RVT, VTS (Equine Veterinary Nursing) Veterinary Technician Specialist Moore Equine Veterinary Centre Rocky View, Alberta, CA Ian Kanda, RVT, VTS (CP-­Exotic Companion Animal) Exotic Veterinary Technician Specialist Pet Hospital of Penasquitos San Diego, CA, USA

Imeldo Laurel, LVT, VTS (Dentistry) Anesthesia and Dentistry Veterinary Technician, Friendship Hospital for Animals Washington, DC, USA Tasha McNerney, CVT, CVPP, VTS (Anesthesia & Analgesia) Founder, The Veterinary Anesthesia Nerds LLC. & Training Director Mt. Laurel Animal Hospital Mt. Laurel, NJ, USA Anne Marie McPartlin, CVT, LVT, RVT Senior Program Coordinator Rural Area Veterinary Services Humane Society of the United States Watertown, NY, USA Margot Monti, CVT, VTS (Zoological Medicine) Veterinary Technician Specialist Oregon Zoo Portland, OR, USA Alison Mott, RVT Hospital Manager and Senior Veterinary Technician, Sacramento Zoo Sacramento, CA, USA

Jessica ­Birdwell, MSMHR, LVMT, VTS (Anesthesia & Analgesia) Veterinary Nursing Director The College of Veterinary Medicine University of Tennessee Knoxville, TN, USA

Stephen Niño Cital, RVT, SRA, RLAT, CVPP, VTS-­LAM (Research Anesthesia) Lab Manager, Howard Hughes Medical Institute at Stanford University, Pain and Cannabinoid Service Director Remedy Veterinary Specialists & Partner, Veterinary Anesthesia Nerds, LLC. San Francisco Bay Area, CA, USA

Katrina Lafferty, CVT, RLAT, VTS (Anesthesia & Analgesia) Senior Anesthesia Veterinary Technician Specialist, Anesthesia and Pain Management Department, Veterinary Medical Teaching Hospital, University of Wisconsin–­Madison Madison, WI, USA

Darci Palmer, LVT, VTS (Anesthesia & Analgesia) Lecturer and Clinical Skills Trainer Tuskegee University College of Veterinary Medicine & Partner Veterinary Anesthesia Nerds, LLC Auburn, AL, USA

List of Contributors

Natalie Pedraja, LVT Practice Manager, UrgentVet – Carytown Richmond, VA, USA Taly Reyes, LVMT, VTS (Anesthesia & Analgesia) Veterinary Nurse Supervisor The College of Veterinary Medicine University of Tennessee Knoxville, TN, USA Karen Maloa Roach, RVT, VTS (ECC) ICU and Training Mentor Mt. Laurel Animal Hospital Mt. Laurel, NJ, USA Brooke Quesnell, CVT, VTS (Oncology) Clinical Education Specialist & Oncology Veterinary Technician Specialist, WestVet Boise, ID, USA Mark Romanoski, CVT, RVT Exotics Department Veterinary Technician Center for Avian and Exotic Medicine Manhattan, NY, USA Robin Saar, RVT, VTS (Nutrition) Sr. Scientific Communication Technician Royal Canin Canada, and Private Nutrition Education Consultant Lethbridge, Alberta, CA Heather Ann Scott, RVT, LVT, VTS (ECC) Technician Learning and Development Specialist, Ethos Veterinary Emergency and Referral Center Hawaii Honolulu, HI, USA

Erin Spencer, MEd, CVT, VTS (ECC) Director of Veterinary Nursing Development Veterinary Emergency Group and Field Veterinary Technician Rural Area Veterinary Services Humane Society of the United States Derry, NH, USA Rachel Stauffer, RVT, LVT, CVT, VTS (ECC) Travel Nursing Manager and RECOVER Coordinator, Veterinary Emergency Group Powhatan, VA, USA Melissa (Missy) Streicher, CVT, VTS (Dermatology) Dermatology Technician, Auburn University College of Veterinary Medicine Auburn, AL, USA Elizabeth (Liz) Vetrano, CVT, VTS (CP-­Exotic Companion) Supervisor, Mt. Laurel Animal Hospital Mt. Laurel, NJ, USA Lindsay Wesselmann, LVT, VTS (Zoological Medicine) Veterinary Technician Alaska Wildlife Conservation Center Girdwood, AK, USA

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Foreword One of the truly great things about getting old is having a long history and, with a little luck, remembering most of it. I began my journey into the world of animal pain management in 1991, long before there was a discipline in veterinary medicine, even before there was much organized thought on the topic. Not a surprise, really, when you consider that there was little understanding of the process or significance of painfulness, not just in animals but also in human medicine where it concerned non-­ or preverbal patients. It seemed our ability to recognize, much less treat, pain even as recently as the end of the twentieth century was limited to the patient’s ability to express it in a language common to caretakers. OUCH! Of course, even when expressed, there were few options and a high incentive to disbelieve the bearer of the pain. In 1991, I was already 10 years into a 13-­year stretch working at the University of Pennsylvania Veterinary Hospital. As head of the ICU, I saw endless “painful” patients and commensurately stressed-­out veterinary support staff. We were certain our patients were suffering but felt up against a wall of resistance to treatment. Perhaps some of you still experience this today. I came to believe that the resistance we met came from a lack of understanding of the importance of treating pain as a disease and the shortage of options at that time. In addition to those barriers, we were never trained to recognize the signs of pain in animal species, especially in those who were evolutionarily determined to hide weakness

from would-­be predators (including veterinary staff armed with medical supplies of all sorts). It was also commonplace to hear mythical comments like “I won’t be able to assess the patient if I drug him,” “I don’t think it’s pain, it’s just her personality,” and perhaps most insidious, “Pain is good because it keeps them from moving around after surgery” (a myth brilliantly debunked by one of my heroes, Dr. Bernie Hanson, DVM, DACVECC, DACVIM, and his team at the University of North Carolina in 1993). As my frustration grew, so did my search for answers. I spent many long hours at the medical library focusing on pain management (or the lack thereof) in neonates and young children, hoping to find answers but finding instead a surprising lack of treatment in those populations as well. Interestingly, whatever information did exist was largely the work of nurses working with parents lobbying for attention to painfulness in their kids. Of course, we do not have the benefit of parents; pet owners are typically not with their pets in the hospital, and at home they do not readily recognize the signs of animal pain. Big “Aha!” moment: This is a nursing issue! I became convinced that this was our fight and began to mobilize. To begin, I conducted a rather simple survey in 1992, sending it to the faculty veterinarians, interns, residents, and students at 10 veterinary schools. I received over 800 responses to the single question on the survey, “How do you know if your patient is in pain?” The results were overwhelmingly

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similar, although as we would later learn, often erroneous: “vocalization, not moving around, not eating” were among the top responses. The single most consistent response, however, was the one that would determine the course of the rest of my career in veterinary medicine. “How do you know if your patient is in pain?” “Because my technician tells me.” I wrote and delivered my first pain management lecture at the International Veterinary Emergency and Critical Care Symposium (IVECCS) in 1994 using an overhead projector and a wax crayon. It was titled “Do Animals Feel Pain?” I was not sure how the topic would be received. Imagine my excitement when the room was packed to standing room only with veterinarians and technicians, all of whom were more than eager to discuss the question. I felt energized by the overwhelming response, and my pain management odyssey was underway. I will fast forward through the next 25 years because you already know the outcome of the story: more formal studies, organizations tasked with looking into the issue, science unraveling the mysteries of pain processing and pharmaceutical companies developing analgesics specifically for animals. For me personally, it meant thousands of worldwide lectures, dozens of publications, many committee

seats and board positions. All of the work was geared toward relentlessly delivering the message to practice the highest standard of animal pain management whether in a premier veterinary academic institution or in the most remote locations in developing countries. Today, animal pain management is a standard of care, and thousands of veterinary professionals are devoted to ensuring their patients are as pain free as possible. The illustrious authors and editors of this work are among them. You are among them. After all, you bought the book! I am now joyfully retired, secure in the knowledge that this vital work continues every day. I have complete faith in the authors and editors of this incredibly comprehensive collection of information. They are among the top experts in the field. The book you are holding will guide you through the recognition and treatment of pain in a huge variety of animal species. It will help you further the mission to provide your patients with the care they deserve. It is a great honor to have contributed to the advancement of animal pain management. Now it is “over to you”! Wishing you and your patients all the best, Nancy Shaffran CVT, VTS(ECC-­ret)

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­Acknowledgments To all the veterinary technicians and assistants that provide excellent care and advocate for your patients, especially those who feel unheard while pushing for change. We hear you. Your patients hear you. Keep it up. –­Stephen Niño Cital I would like to thank my husband, Rob, who is better at U/S guided blocks than I am, for always encouraging me to shoot for the stars and never turning down my last-­minute travel ideas. To my son Oliver, because your default emotion is kindness, and I am so, so proud of the human you are turning into. To Darci and Stephen. What can I say? The best travel companions, the best friends…Dulce Leche! To Nancy Shaffran, MaryEllen Goldberg, and Vickie Byard…you are the inspirations in every way. Thank you for making veterinary medicine better. Thank you for making me better. –­Tasha McNerney To the past, present, and future veterinary ­students that I encounter on a daily basis  – Thank you for inspiring me to never stop

l­ ooking for better ways to promote best practices in veterinary anesthesia and analgesia. To my mentors and fellow veterinary colleagues  – Thank you for the encouragement and motivation to strive to learn something new each and every day. To my husband Lee and our boys, Cody, and Zach – Thank you for your support, love, and understanding for when I take on all these crazy projects. –Darci Palmer And to all the Veterinary Anesthesia Nerds, This book is ultimately dedicated to you. Your insatiable curiosity and thirst for knowledge have propelled the industry forward, inspiring countless veterinary professionals to continually seek improvement and innovation in the field. Your tireless efforts have not only alleviated the suffering of countless animals but have also advanced the quality of care provided by veterinary professionals worldwide. Thank you for your passion, your endless curiosity, and your relentless dedication to patient care. –Tasha, Darci, and Stephen

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About the Companion Website This book is accompanied by a companion website:

www.wiley.com/go/mcnerney/2e  This website includes: ●●

Videos

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1 Advancing Veterinary Pain Management into a New Era Mary Ellen Goldberg Independent Contractor & Mannheimer Foundation Inc., Boynton Beach, FL, USA

“The greatest evil is physical pain.” Saint Augustine of Hippo (386)

1.1 ­Introduction A living being, from the moment of birth, seeks pleasure as the ultimate good while rejecting pain as the ultimate adversity and does their best to avoid it. Pain is based on an anatomical and physiological foundation. It is the intent of this chapter to historically look at human pain, proceed forth into veterinary pain, and conclude with a veterinary technician’s pivotal role moving forward in pain management today.

1.2  ­Brief History of Human Pain Management Western cultural identity has, in part, been influenced by ancient Greek texts such as The Iliad and The Odyssey by Homer because of the emphasis these stories placed on pain. Sophocles continues to describe pain almost as an independent being that seizes possession of the subject, invades it, and takes over. Thus, words like consuming or devouring are used to

describe the ill being (Rey  1993). Galen of Pergamon was a Greek physician, surgeon, and philosopher in the Roman Empire. Galen is known today for classifying the different forms of pain which have been handed down to modern times: Pulsific or throbbing, gravative or weighty, tensive or stretching, and pungitive or lancinating (Rey 1993). In contrast to Western medicine, which can be traced back to Hippocrates, Chinese acupuncture was fully developed by the end of the second century bce (before the common era). Among many ancient civilizations, such as kingdoms in Africa, Sumer, China, Mesoamerica, and the Indus-­Ganges, China is the only civilization where acupuncture was well documented 2000 years ago that still survives (Chiu 2014). Before the advent of modern anesthesia, humans used diverse means to diminish pain, including pressure or ice to numb extremities. Many indigenous cultures had their own understanding of pain and often took a more holistic approach to managing discomfort, something that we see a reawakening of today. They administered herbal medicines including mandragora, hemp-­marijuana, and opium. Some used fermented drinks that contained alcohol used not only for pain but also for ceremonies and recreation. The Incas, as an example, knew of the

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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topical effects of coca/cocaine leaves, but they had no way to administer it other than placing coca-­laced saliva into wounds. Hua Tuo (in the second century ce) was a Chinese physician and surgeon who is best known for his surgical operations and the use of mafeisan, an herbal anesthetic formulation made from hemp. Using a preparation of hemp and wine, he was able to make his patients insensitive to pain (Tubbs et  al.  2011). Other Mesoamerican Indigenous and Aboriginal Australian people not only used herbal and mechanical means for pain relief but also incorporated ceremony, showing a deep understanding of the interconnection between physical, emotional, and ­spiritual health in all creatures. Unfortunately, many of these ancient herbal remedies and other culturally significant practices were banned or lost during colonization, only to be “rediscovered” in modern times by the same but very distant relatives of the ­original colonizers. The loss or suppression of indigenous ­peoples’ healing practices leaves us with a “Western” or “Eurocentric” perspective in textbooks on the evolution of pain management (Eger et  al.  2014; Geck et  al.  2020; Quiñonez-­Bastidas and Navarrete  2021; Carmona Rosales 2021; Wren et al. 2011). René Descartes, a French scientist and ­philosopher, was the first recorded person to claim that pain comes from the brain. His study focused on phantom limb pain and since there was no limb to feel pain, he concluded that pain must come from the brain. Descartes opened the door to the understanding that the  brain was a key component of pain, though it would be centuries before the complete ­connection between the brain, nervous system, and pain was made (Rey 1993). Albrecht von Haller was interested in the reactions of fibers and how to distinguish between the irritability of muscle fiber – which he called contractibility  – and the excitability of nerve fibers  – which he called sensitivity (Olson 2013a). Pierre Jean George Cabanis’ work incorporated a psychophysiological approach to pain, which included the emotional component. His

work led to new techniques such as using electrical stimulation for the treatment of pain. Xavier Bichat represented a passage from organic sensitivity to animal sensitivity and the threshold concept. Bichat’s contribution to pain medicine was his discovery of the importance of the sympathetic nervous system (Olson 2013a). The early part of the nineteenth century saw the development of health clinics, which increased interest in the study of pain. Pain research at this time remained within the framework of specificity theory advanced by Johannes Müller and later Maximilian von Frey, which saw pain as an independent sensation with its own sensory apparatus. Müller proposed a theory for pain, which considered findings from physiology, historical observations, pathology, and integrated psychological dimensions of pain. He believed that pain was not imaginary  – that it could occur without an  external stimulus. Von Frey was trying to ­identify points on the skin that responded ­specifically to one of the four cutaneous sensations: touch, heat, cold, and pain. To accomplish this task, he invented what he called an esthesiometer, where the stimulus consisted of hair (Olson 2013b). In 1965, Ron Melzack and Patrick Wall proposed a theory suggesting that neural mechanisms in the dorsal horn of the spinal cord could act as a “gate,” increasing or decreasing the flow of nerve impulses from peripheral fibers to the spinal cord cells projecting to the brain. In other words, the spinal cord “gate” either blocks pain signals or lets them pass onto the brain (Melzack and Wall 1965). Today, the gate control theory continues to thrive and evolve despite considerable controversy. The technology of spinal cord stimulation is also based on the gate control theory where products approved by the FDA are already on the market. In 1973, John Bonica, the founding father of the modern-­day field of pain medicine and the driving force in establishing the International Association for the Study of Pain (IASP), proposed that relief of pain is a basic human right (Jackson and Norman 2014).

1.4 ­Animal Research Contributions

1.3 Veterinary Pain Management Through the Centuries The surviving records on the advancement of veterinary medicine occurred during the Greek, Roman, and Byzantine eras. During this period, many species were investigated, with primary attention paid to the horse. The development of nailed-­on horseshoes was a major technological step that enhanced the performance of draft and cavalry horses in the Dark Ages. The Celts were first to use red hot iron to fit under the strong rim of the horse’s hoof. The Islamic world chose lighter shoes that could be shaped cold (Dunlop and Williams 1996). During the Middle Ages, mandragora (or the root of the mandrake plant) was made into an anesthetic potion administered to the patient (human or animal) before surgery or cautery (Eger et al. 2014). It induced a deep sleep likely due to the plants natural production of deliriant hallucinogenic tropane alkaloids (atropine, scopolamine, and hyoscyamine) (Roberts and Wink 1998). In 1656, Christopher Wren (the architect for St. Paul’s cathedral and a founder of the Royal Society) infused wine and ale from a syringe made of a dog’s bladder, through a goose quill needle into the vein of a dog. The dog survived the experiment. Wren later gave opium intravenously via a quill to dogs, causing unconsciousness in some animals, but killing others. Wren’s experiment was the first known injection to produce anesthesia (Moon 2021). Gasses and vapors later known as anesthetics had been synthesized or isolated before (ether, nitrous oxide, and carbon dioxide) but would be more regularly synthesized from 1798 through 1846 for research and medical use. In 1798–1800, Humphry Davy used nitrous oxide for recreation and research, noting its capacity to diminish or even abolish pain. He suggested its use for surgery, but no one noticed (Ramsay et  al.  2005). In 1823, Hickman used carbon dioxide to cause what he called “suspended animation,” a state that

permitted apparently painless surgery in animals, but no one noticed (Eger et al. 2014). In the 1840s, William Clarke, Crawford Long, and Elton Romeo Smilie each administered ether in amounts sufficient to permit surgery to be undertaken without pain. But they thought too little of what they had done, or didn’t know what they had done, to request public credit for their accomplishment and no one noticed (Keys 1996). Veterinary anesthesia/analgesia has paralleled human anesthesia/analgesia for the most part, but also still lags in many ways. The two have been intimately intertwined, each contributing to the advancement of the other. The introduction of veterinary anesthesia was delayed by the misperception that the induction of anesthesia in animals was painful and unnecessary, one needed to only “hobble” the animal, in other words, forcefully restrain. This misperception gave way to the governmental demand for the application of anesthesia to relieve the pain of surgery in animals. The performance of anesthesia and surgery in animals today is remarkably like that in humans, particularly in the United States, Great Britain, and Europe (Steffey 2014).

1.4 Animal Research Contributions Humans have been using other animal species as models of their anatomy and physiology since the dawn of medicine. Because of the taboos regarding the dissection of humans, physicians in ancient Greece dissected animals for anatomical studies (Franco 2013). Jeremy Bentham was the first person to grant animals moral standing for the sake of their own sentience. He stated, “The question is not, can they reason? Nor, can they talk? But can they suffer?” (Bentham 1789). Charles Darwin was known for his affection to animals and abhorrence for any kind of cruelty, but also for his commitment to scientific reasoning and progress (Franco 2013).

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Joseph Lister pointed out the importance of animal experiments for the advancement of medical knowledge, stressed that anesthetics should always be used, and denounced the ill-­ treatment of animals in sports, cruel training methods, and artificial fattening of animals for human consumption as being crueler than their use in research (Gaw 1999). While animal experiments have played a vital role in scientific and biomedical progress and are likely to continue to do so in the foreseeable future, it is nonetheless important to keep focusing on the continuous improvement of the well-­being of laboratory animals, as well as further development of replacement alternatives for animal experiments (Franco 2013). Pain is a major welfare issue in animal experiments and must be treated and minimized for ethical and scientific reasons. Unrelieved pain may have a substantial and difficult-­to-­control effect on many physiological processes and behaviors. Pain has the potential to increase the variability of data. Untreated pain may affect complex behavioral traits such as circadian rhythmicity or decision-­making, attention, and learning via motivational changes, and may change the sensory capacities of animals via allodynia and hyperalgesia or affect many physiological and endocrine systems (Jirkof  2017). Thus, adequate pain relief has an important scientific and methodological dimension.

1.5 History of Animal Nursing Staff Through the years, individuals have aided veterinarians in the care provided to animals. Spouses, family members, and other laypersons served as assistants, receptionists, and office managers for the veterinary practice. The first record of a program for training, other than for veterinarians, occurred in 1908 with the formation of the Canine Nurses Institute in the United Kingdom (Turner & Turner 2011). The term veterinary technician is commonly used in the United States and Canada, whereas

veterinary nurse is uniformly used in countries throughout Europe and Asia. Veterinary technicians were first called animal health technicians in the United States and Canada. The adjective veterinary referred exclusively to veterinarians until 1989, when the term veterinary technician was formally approved by the House of Delegates of the American Veter­ inary Medical Association (AVMA) (Bassert and Lazo 2021). The designations in the United States are Registered Veterinary Technician (RVT), Licensed Veterinary Technician (LVT), Certified Veterinary Technician (CVT), or Licensed Veterinary Medical Technician (LVMT); depending on where in the United States one lives. Animal Health Technicians or Registered Veterinary Technicians/Technologists is the term used for those living in Canada. This is governed by the individual Canadian Province. The term for those in Europe and some Asian countries is Registered Veterinary Nurse (RVN). The National Association of Veterinary Technicians in America (NAVTA) in the mid-­ 1990s developed the Committee on Veterinary Technician Specialties (CVTS) to help guide and structure the development of specialties for  credentialed veterinary technicians. The CVTS provides a standardized list of criteria and assistance for societies interested in attaining academy status. Each Veterinary Technician Specialist (VTS) has completed requirements of formal education, clinical training, and standardized testing within their specialty area of interest (Bassert and Lazo 2021).

1.5.1 National Association of Veterinary Technicians in America Recognized Veterinary Technician Specialty Academies The Academy of Veterinary Emergency and Critical Care Technicians The Academy of Veterinary Dental Technicians The Academy of Internal Medicine Veterinary Technicians

1.6 Eyewitneeeto  50 eareoof Cangeeofor Veterinary ecCniciane

The Academy of Veterinary Technicians in Anesthesia and Analgesia The Academy of Laboratory Animal Veterinary Technicians and Nurses The Academy of Veterinary Behavior Technicians The Academy of Veterinary Clinical Pathology Technicians The Academy of Veterinary Technicians in Clinical Practice The Academy of Dermatology Veterinary Technicians The Academy of Equine Veterinary Nursing Technicians The Academy of Physical Rehabilitation Veterinary Technicians The Academy of Veterinary Nutrition Technicians The Academy of Veterinary Ophthalmic Technicians The Academy of Veterinary Surgical Technicians The Academy of Veterinary Zoological ­Medicine Technicians The Academy of Veterinary Technicians in Diagnostic Imaging

1.6 Eyewitness to 50 Years of Changes for Veterinary Technicians The author of this first chapter has been involved in veterinary medicine since 1971, beginning in high school working on weekends, holidays, and summer vacations, until she went to an accredited AVMA approved program in the fall of 1974. Over this time, there was relatively no pain management or analgesia practiced in veterinary medicine. The author was at the University of Pennsylvania’s School of Veterinary Medicine and New Bolton Center, Large Animal Veterinary School located in Kennett Square, Pennsylvania, from 1974–1976. It was not uncommon to hear the equine surgeons state, “I want my patients to have pain to prevent movement that would damage my work.”

Since graduation, the author has worked in various aspects of veterinary medicine from small animal and equine to mixed practice, coccidiosis research for a pharmaceutical company, zoo animal medicine, and laboratory animal medicine. This author can remember the first time pain relief was mentioned during her veterinary career. It was in the use of methoxyflurane (Penthrane® – Abbott Laboratories, Chicago, Illinois). This inhaled anesthetic was “better for orthopedic surgery because it provided analgesia” (remembered quote). In the textbook Principles and Practice of Veterinary Anesthesia, methoxyflurane is referred to: “At light surgical planes of anesthesia or more, profound analgesia is present” (Short  1987). Its  clinical role gradually decreased in the 1970s because of reports of dose-­dependent nephrotoxicity. In 1999, its manufacturer, Abbott Laboratories, discontinued the distribution of methoxyflurane in the United States and Canada. Outside of North America, however, methoxyflurane has been reborn as an  inhaled human analgesic used for pain relief in the prehospital setting and for minor surgical  procedures. First used in Australia and New Zealand, and subsequently in over 37 other countries, low concentrations of methoxyflurane are administered with a hand-­held inhaler that provides conscious sedation (Ikeda 2020). Injectable anesthetics and analgesics in veterinary medicine started with ketamine. The history of ketamine begins in the 1950s at Parke-­Davis and Company’s laboratories in Detroit, Michigan, USA. At that time, Parke-­ Davis was searching among cyclohexylamines for an “ideal” anesthetic agent with analgesic properties (Mion 2017). It was regularly used on dogs and horses and extensively used for surgical anesthesia during the Vietnam War (Domino  2010). Ketamine has been used in cats since this author can remember (early 1970s). Ketamine when used alone produces immobilization but not surgical anesthesia. It  induces a state of

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catalepsy or dissociative anesthesia (Thomas et al. 2021). Today, it is commonly used in the perioperative setting in anesthetic planning for sedation, in combination with other drugs for induction, intra-­op infusion, and postoperative pain management. In the 1980s, the only “analgesics” used were local anesthetics and alpha-­2-­antagonist agents. The author can remember the first bottle of butorphanol purchased for orthopedic surgery. Butorphanol was not a scheduled or controlled substance in 1988. In fact, butorphanol under the trade names Torbugesic® and Torbutrol® was first marketed as an injectable product in 1979. The veterinary product was marketed by Fort Dodge Animal Health, and the human product, under the trade name Stadol®, was marketed by Bristol-­Myers Squibb. The Federal Register Volume 62, Number 190 (Wednesday, October 1, 1997) placed butorphanol into a Schedule IV category by the Drug Enforcement Administration, Department of Justice (Federal Register 1997). The use of analgesics has grown by leaps and bounds over the past 50 years in the veterinary profession. The variety of analgesics available for use in the United States is vast. European countries have a wide variety of analgesics, too. However, it should be noted that not all countries globally have access to newer analgesics.

1.7 Veterinary Technician Pioneers in Pain Management No history of veterinary analgesia use would  be  complete without the mention of Nancy Shaffran CVT, VTS-­ECC (Veterinary Technician Specialist, Emergency and Critical Care). Nancy is a professional veterinary educator with an extensive background in critical care and pain management. She graduated from the University of Pennsylvania. She is a charter member and a past president of the Academy of Veterinary Emergency and Critical

Care Technicians and Nurses. After 12 years at  the University of Pennsylvania Veterinary Hospital, where she was the supervisor of the intensive care unit, Nancy spent 5 years as director of Education and Staff Relations at Cardiopet’s Veterinary Referral Center followed by 7 years as a senior specialist on the sedation and pain management team at Pfizer Animal Health, now Zoetis Animal Health. Nancy has given over 2500 lectures to technicians and veterinarians around the world. She has authored more than 25 journal articles and book chapters besides editing books. The focus of Nancy’s career has been the ethics and appropriate management of pain in companion animals. *Editor’s Note: The editors would also like to acknowledge the tremendous efforts of the author of this chapter, Mary Ellen Goldberg, for her passion and dedication to the field of animal care, particularly in the fields of ­veterinary anesthesia, pain management, and physical rehabilitation. Mary Ellen was critical in the development and administration of the  Certified Veterinary Pain Practitioner (CVPP) certification through the International Academy of Pain Management (IVAPM) and an organizing member for two of the veterinary technician specialty academies. Because of her dedication, she also received an honorary veterinary technician specialty from the  Academy of Veterinary Technicians in Anesthesia and Analgesia. Mary Ellen is known worldwide for her selfless dedication and contribution in pushing for the advancement of veterinary nursing staff and education within the veterinary profession.

*  The editors would like to acknowledge and give credit to the numerous humans that were enslaved and/or inhumanely used for the ­purposes of discovery in medical science. Their suffering and contributions to the advancement of both human and animal medical care are immeasurable and deserve recognition.

­eoferencee

1.8 ­Future Directions for Veterinary Technician Pain Management Innovative trends in veterinary pain management will require advanced skills that would need specialization before the technician would be allowed to perform any techniques. Most of these medications and techniques are  new to specialized veterinarians. One can  already envision with educational and clinical training, that specialized veterinary technicians may be able to provide these therapies as directed by the veterinarians. The advent of various specialty certifications like the veterinary technician specialties or CVPP from the IVAPM, or certificate programs like those from the World Small Animal Veterinary Association and American Animal Hospital Association offer veterinary technician’s routes to grow professionally. We are also at a precipice for increasing the scope of practice for veterinary technicians with a VTS as multiple states have already increased the scope of practice for veterinary technician’s specialists, which will allow for an

increased access to care, particularly animals that need chronic pain case management.

1.9 Conclusion Our increasing knowledge of the mechanisms and factors related to the multidimensional nature of pain has been translated into an improved understanding of the care for our veterinary patients in pain. We have improved surgeries, interventional procedures, medications, behavioral interventions, physical rehabilitation, acupuncture, and nutritional approaches. We also have a greater appreciation for the need for an interdisciplinary (­veterinarian, veterinary technician/nurse, veterinary assistant, physical therapist, veterinary acupuncturist, veterinary behaviorist, veterinary nutritionist) team-­based approach to optimize pain care, particularly for more complex cases. As we move into a new era of veterinary pain management, let us hope that we will begin to achieve our goal to have each of our patients be as pain-­free as possible.

References Augustine, T. (386). Soliloquies of St. Augustine of Hippo, vol. vol. I, 21. Reprinted by. Dalcassian Publishing Company, 2023. Bassert, J.M. and Lazo, T. (2021). Introduction to veterinary nursing and technology. In: McCurnin’s Clinical Textbook for Veterinary Technicians and Nurses, 10e (ed. J.M. Bassert, A.D. Beal, and O.M. Samples), 3–4. St. Louis, MO: Elsevier, Inc., 13. Bentham, J. (1789). An Introduction to the Principles of Morals and Legislation, 122. London: W. Pickering, ch. 7,. Carmona Rosales, J. (2021). Sacred herbs and ancient healers: decolonizing traditional mexican medicinal practices. FIU Electronic Theses and Dissertations, No. 4635.

Chiu, J.H. (2014). History of acupuncture. In: Acupuncture for Pain Management (ed. Y.C. Lin and E.Z. Hsu). New York, NY: Springer https://doi.org/10.1007/978-­1-­4614-­ 5275-­1_1. Domino, E.F. (2010). Taming the ketamine tiger. Anesthesiology 113 (3): 678–684. https://doi.org/ 10.1097/ALN.0b013e3181ed09a2. Dunlop, R.H. and Williams, D.J. (1996). Animals in the dark ages. In: Veterinary Medicine: An Illustrated History (ed. M.O. St Louis), 203–235. Mosby-­Yearbook, Inc. Eger, E.I. II, Saidman, L.J., and Westhorpe, R.N. (2014). History to 1798. In: The Wondrous Story of Anesthesia, 3–10. New York, NY: Springer.

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Federal Register Online (1997). FR Doc No: 97-­25969. pp. 51370–51371. https://www. deadiversion.usdoj.gov/fed_regs/rules/prior_ 1998/fr1001_1997.htm Franco, N.H. (2013). Animal experiments in biomedical research: a historical perspective. Animals 3: 238–273. Gaw, J.L. (1999). “A Time to Heal”: The Diffusion of Listerism in Victorian Britain, 1–173. Philadelphia, PA: American Philosophical Society. Geck, M.S., Cristians, S., Berger-­Gonzalez, M. et al. (2020). Traditional herbal medicine in Mesoamerica: toward its evidence base for improving universal health coverage. Frontiers in Pharmacology 11: 1160. https://doi.org/ 10.3389/fphar.2020.01160. Ikeda, S. (2020). The reincarnation of methoxyflurane. Journal of Anesthesia History 6 (2): 79–83. https://doi.org/10.1016/j.janh. 2019.07.001. Jackson, S.H. and Norman, G.V. (2014). Anesthesia, anesthesiologists, and modern medical ethics. In: The Wondrous Story of Anesthesia. https://doi.org/10.1007/978­1-­4614-­8441-­7_17 (ed. E.I. Eger II et al.), 207. Springer. Jirkof, P. (2017). Side effects of pain and analgesia in animal experimentation. Lab Animal 46 (4): 123–128. Keys, T.E. (1996). The History of Surgical Anesthesia, 21–22. Park Ridge: Wood Library-­ Museum of Anesthesiology. Melzack, R. and Wall, P.D. (1965). Pain mechanisms: a new theory. Science 150 (3699): 971–979. Mion, G. (2017). History of anaesthesia -­the ketamine story – past, present, and future. European Journal of Anaesthesiology 34: 571–575. Moon, J.S. (2021). The circle of life: Christopher Wren and the first intravenous anesthetic. Anesthesiology 135: 520–530. Olson, K. (2013a). History of pain: a brief overview of the 17th and 18th centuries. https://www.practicalpainmanagement.com/ pain/history-­pain-­brief-­overview-­17th-­18th-­ centuries (accessed 25 May 2024).

Olson, K. (2013b). History of pain: a brief overview of the 19th and 20th centuries. https://www.practicalpainmanagement.com/ treatments/history-­pain-­brief-­overview-­19th­20th-­centuries (accessed 25 May 2024). Quiñonez-­Bastidas, G.N. and Navarrete, A. (2021). Mexican plants and derivates compounds as alternative for inflammatory and neuropathic pain treatment-­a review. Plants (Basel) 10 (5): 865. https://doi.org/ 10.3390/plants10050865. Ramsay, D.S., Leroux, B.G., Rothen, M. et al. (2005). Nitrous oxide analgesia in humans: acute and chronic tolerance. Pain 114: 19–28. Rey, R. (1993). ‘Antiquity’, in History of Pain, 24. Paris: La Decouverte. Roberts, M.F. and Wink, M. (1998). Alkaloids: Biochemistry, Ecology, and Medicinal Applications, 34. New York: Plenum Press. Short, C.E. (1987). Inhalant anesthetics. In: Principles and Practice of Veterinary Anesthesia (ed. C.E. Short), 70–90. Baltimore, MD: Williams and Wilkins. Steffey, E.P. (2014). A history of veterinary anesthesia. In: The Wondrous Story of Anesthesia. https://doi.org/10.1007/978-­1-­ 4614-8441-­7_23 (ed. E.I. Eger II et al.), 293–302. Springer. Thomas, J.A., Lerche, P., Cruea, H. et al. (2021). Veterinary anesthesia. In: McCurnin’s Clinical Textbook for Veterinary Technicians and Nurses, 10e (ed. J.M. Bassert, A.D. Beal, and O.M. Samples), 925–972. St. Louis, MO: Elsevier, Inc. Tubbs, R.S., Riech, S., Verma, K. et al. (2011). China’s first surgeon: Hua Tuo (c. 108–208 AD). Childs Nervous System 27: 1357. https://doi. org/10.1007/s00381-­011-­1423-­z. Turner, T. and Turner, J. (2011). VN Jubilee Seminar – ‘Looking Back, Stepping Forward. www.rcvs.org.uk/document-­library/jubilee-­ seminar-­trevor-­and-­jean-­turner-­presentation (accessed 25 May 2024). Wren, A.A., Wright, M.A., Carson, J.W. et al. (2011). Yoga for persistent pain: new findings and directions for an ancient practice. Pain 152 (3): 477–480. https://doi.org/10.1016/ j.pain.2010.11.017.

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2 Careers in Animal Pain Management Tasha McNerney1,2 and Stephen Niño Cital1,3,4 1 

The Veterinary Anesthesia Nerds, LLC., Sheridan, WY, USA Mt. Laurel Animal Hospital, Mt. Laurel, NJ, USA 3  Howard Hughes Medical Institute at Stanford University, Stanford, CA, USA 4  Remedy Veterinary Specialists, San Francisco, CA, USA 2 

2.1 ­Introduction As professionals, one of the main reasons we all go into this field is to ease animal suffering, in essence, to prevent pain. Whether you realize it or not, we are all stewards of proper pain management for our veterinary patients and have a responsibility to keep abreast of the latest advances in animal pain management from a pharmacological, physical, and psychological perspective. Today, veterinary technicians/veterinary nurses (international) can pursue further training and specialization in many areas, including but not limited to dentistry, anesthesia, internal medicine, emergency and critical care, and pain management. Collaborative approaches between veterinary nursing staff and veterinarians on pain management, among all the other aspects of animal health care, help strengthen the practice’s culture and the bond between animals and their owners. Pain management has become an important specialty in human medicine, leading to a greater awareness of pain in animals. Pet parents want the best for their

non-­human family members, including top-­of-­ the-­line pain management. As alluded to above, we now know that pain is best managed through an interdisciplinary approach, and we can best achieve effective pain management through animal healthcare team cooperation, the sharing of knowledge, and the collective wisdom of veterinary professionals from many disciplines. There are many different programs and certifications that veterinary technicians and nurses can participate in to expand their knowledge and skills when it comes to pain management. Here we review some of the options currently available.

2.2 ­Pain Management Certifications Available for Veterinary Technicians/Nurses 2.2.1  Certified Veterinary Pain Practitioner (CVPP) The IVAPM certification program is designed to represent a moderate-­to-­advanced level of competence as an interdisciplinary pain

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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practitioner while providing the platform and incentive for  continued and expanded ­learning in the field of veterinary pain management. The current program will lead to the credential as a Certified Veterinary Pain Practitioner (CVPP) for veterinarians and credentialed veterinary technicians or nurses; or a Certified Animal Pain Practitioner (CAPP) for physical therapists and physical therapist assistants with certification in canine rehabilitation. The IVAPM certification program is intended to emphasize the value of the many disciplines capable of enhancing patient comfort and quality of life and to facilitate an understanding of the modalities not necessarily in the member’s current area of familiarity. IVAPM hopes to facilitate the networking of professionals engaged in allopathic modalities, physical rehabilitation, and complementary alternative therapies. IVAPM in general, and the CVPP/CAPP in particular, provide the stage upon which all professionals committed to promoting, enhancing, and advancing pain management in animals may interface. It is a foundation upon which the veterinary profession can build the most effective multidisciplinary pain management team. After obtaining a CVPP, the veterinary technician can work with pet owners and veterinarians to provide the best pain management plans for patients by following these practices: 1) Assess the patient’s status and pain management scheme together with the owner and veterinarian and then create a pain management plan specific to that patient for the best overall outcome. 2) Assist in the acute pain management setting, helping clinics to create protocols under a veterinarian’s guidance for postoperative pain scoring and proper analgesic techniques for acute surgical pain. 3) Act as a point person whom the pet owner can contact and relay information to about the pet’s progress. The CVPP can then take this information and work with the veterinarian to make changes to the analgesic

plan as necessary to ensure the best ­outcome for that patient. 4) Lead a “pain service” within a practice. A pain service focuses care on chronic pain cases, where regular follow-­up and adjustments to protocols are more closely followed. By obtaining your CVPP, you can also help in the continuing education of your clients and team members. Many veterinary professionals who have obtained the CVPP credential go on to write magazine articles, teach online courses, and lead seminars on various pain management topics. Full details about the process for this certification are available on the IVAPM website. www.ivapm.org

2.2.2  Veterinary Technician Specialist (Anesthesia and Analgesia), and Veterinary Technician Specialist (Laboratory Animal Medicine – Research Anesthetist) Perhaps one is interested in seeing physiology in action on an anesthesia monitor during surgical procedures. If your interests align more with anesthesia and all the stages before and  after relating to analgesia, then obtaining your specialty in anesthesia and analgesia may  be a path to consider. The Academy of  Veterinary Technicians in Anesthesia & Analgesia (AVTAA) and The Academy of Laboratory Animal Veterinary Technicians and Nurses (ALAVTN) exist to promote interest in the discipline of veterinary anesthesia and analgesia. The academies provide a process by which a credentialed veterinary technician or nurse may become credentialed as a Veterinary Technician Specialist (VTS) in anesthesia and analgesia (with the AVTAA) or as a research anesthetist (with the ALAVTN) through an application process that includes case logs, skills assessment, case reports, and CE hours along with a comprehensive exam. The academies provide the opportunity for members to enhance their knowledge and

2.2 PainManagementCertiiiiatiinsAAailaaleiir eterinarry eicniiianss/Nrses

skills in the field of veterinary anesthesia and  analgesia. A veterinary technician who becomes certified as a VTS (Anesthesia & Analgesia) or VTS (Research Anesthesia) demonstrates superior knowledge in the care and management of anesthesia cases especially where it pertains to anesthesia and acute (surgical) analgesia. A VTS is responsible for perioperative pain management such as formulating a multimodal analgesic drug protocol, setting up analgesic continuous rate infusions, and performing local and regional analgesia techniques. The veterinary anesthesia/pain management arena is constantly evolving; thus, the VTS (Anesthesia & Analgesia) or VTS (Research Anesthesia) requires members to re-­credential every five years. www.avtaa-­vts.org www.alavtn.org

2.2.3  Veterinary Technician Specialist (Physical Rehabilitation) This academy provides a process by which a credentialed veterinary technician or nurse may become credentialed as a VTS in physical rehabilitation through an application process that includes case logs, skills assessment, case reports, and CE hours along with a comprehensive exam. Veterinary physical rehabilitation plays a crucial role in the comprehensive pain management plan for our patients, ensuring a well-­rounded approach to their well-­being. Integrating physical rehabilitation into their care not only addresses pain but also promotes faster recovery and improved quality of life. www.aprvt.com

2.2.4  Surgical Research Anesthetist (SRA) If you have ever thought about being a part of a team on the cutting edge of new analgesic research, perhaps a career as a surgical research anesthetist is your calling. Founded in 1982, the Academy of Surgical Research promotes the advancement of professional and academic standards, education, and research

in the arts and sciences of experimental ­surgery. The Academy interfaces with medical and scientific organizations, and governmental agencies in ­establishing and reviewing ethics, theories, practices, and research on surgery, anesthesia, and analgesia and promoting the results for clinical application. The SRA certification is intended for the veterinarian, veterinary technician/nurse, graduate student, or research assistant who works as an anesthetist and who also has responsibilities as part of the research surgical team that include aseptic preparation and perioperative care of surgical patients. This includes preoperative analgesic planning, intra-­operative care, post-­procedure pain scoring, and continued assessment of analgesia needs. The SRA candidate must have documented experience with at least two species as reflected in an anesthetic case log. www.surgicalresearch.org

2.2.5  The University of Tennessee Companion Animal Pain Management Certificate Program The program is a 28-­hour online, on-­demand course for veterinarians and veterinary technicians. This course is designed to help participants identify the pathologies that will benefit from effective pain management practices. It provides an in-­depth discussion of the neurobiology of acute and chronic pain. www.utvetrehab.com/product/capm

2.2.6  AAHA Pain Management Guidelines Certificate Course (AAHA Pain Management Champion) Pain management guidelines are constantly evolving. This new 4-­hour course (released in 2023) allows veterinary professionals to  take modules based on the American Animal Hospital Association (AAHA) Pain Management Guidelines that are released every 2-­3 years. www.aaha.org

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2.2.7  WSAVA Certificate in Pain Management The World Small Animal Veterinary Association (WSAVA) certificate is centered around the WSAVA Global Guidelines for the Recognition, Assessment, and Treatment of Pain. This is a modularized program released in 2023 that can be used for general pain-­focused education, or one can finish all the modules and take an exam for the certification. www.wsava.org

2.2.8  Canine Rehabilitation Veterinary Technician Certifications Rehabilitation therapy is an important cornerstone for both acute and chronic pain management. There are two institutions where the veterinary technician can become certified in canine rehabilitation: A) Canine Rehabilitation Institute  – The Certified Canine Rehabilitation Veterinary Technician or Nurse (CCRVT or CCRVN) is for veterinary technicians/nurses with a focus on physical means of providing pain relieving care through strength training, mobility exercises, stretching, and other physical therapy methods. http://www. caninerehabinstitute.com B) The University of Tennessee  – Certified Canine Rehabilitation Practitioner (CCRP) program. Aimed at professionals in the fields of veterinary medicine and physical therapy, they seek to provide information that will assist those exploring the field of canine rehabilitation to those already pursuing it through practice and/or research. http://www.utcaninerehab.com

2.2.9  Equine Rehabilitation Veterinary Technician Certifications Currently, there are three institutions offering certification in Equine Rehabilitation in North America: A) Animal Rehab Institute – Certified Equine Rehabilitation Assistant (CERA) offered to

veterinary technicians and physical therapist assistants. Veterinary continuing ­education units (CEUs) are currently being applied for through the American Veterinary Medical Association (AVMA). http://www.animalrehabinstitute.com B) The University of Tennessee offers The Equine Rehabilitation Certificate Program (CERP) in cooperation with Colorado State University Orthopedic Research Center. www.utvetrehab.com C) The Animal Rehabilitation Institute in Loxahatchee, Florida, offers credentialed veterinary technicians the designation of CERA. https://animalrehabinstitute.com/

2.2.10  Certified Equine Massage Therapist Equine massage therapy certification provides students the skills necessary to perform a full-­ body assessment and massage treatment incorporating effleurage, petrissage, tapotement, friction, vibration, trigger point, stress point, and myofascial release techniques on the horse. No indication of veterinary CEU is indicated. www.animalrehabinstitute.com

2.2.11  Animal Acupressure and Massage The National Board of Certification for Animal Acupressure and Massage (NBCAAM) supports the world of animal acupressure and massage by setting high standards for entry into the field, ensuring animal owners have highly trained practitioners available. The NBCAAM provides certification exams for equine acupressure and massage, and canine acupressure and massage, as well as networking and legislative assistance for practitioners, students, and schools. www.nbcaam.org

2.2.12  TCVM Veterinary Technician Programs Offered by the Chi Institute Traditional Chinese Veterinary Medicine (TCVM) for Veterinary Technicians is a program designed to teach veterinary technicians

2.2 PainManagementCertiiiiatiinsAAailaaleiir eterinarry eicniiianss/Nrses

to support and promote TCVM services in practice. Through the program, techs are given the tools to speak knowledgeably about the purpose and value of TCVM and to teach clients how to care for their animals with food therapy and Tui na techniques. There is no certification available through this course. The purpose is to  teach the technician/nurse about the five areas of TCVM: acupuncture, Tui na, herbal ­medicine, food therapy, and Qigong. www.chiu.edu

2.2.13  Animal Acupuncture There is a common misconception that only veterinarians are allowed to perform acupuncture. This is not true in all states or countries. Many states in the USA allow trained veterinary technicians or human acupuncturists to perform acupuncture under various levels of supervision outlined in an individual state practice act. The veterinarian is still required to make a diagnosis and provide orders as to where anatomically the needling is to take place. Unfortunately, there are no formal programs that veterinary technicians can take to certify them as veterinary acupuncturists, and training is generally limited as to how far a veterinary technician can advance in the courses that are designed for veterinarians.

2.2.14  Low-­Stress Certifications There are many options and programs available now to help advance veterinary professionals when it comes to creating an environment of low stress and anxiety to facilitate safer ­veterinary visits and strengthen the human– animal bond. Stress, anxiety, and fear contribute to negative experiences and can increase the severity of the pain response. As veterinary professionals, any additional education and experience we can get to help alleviate this fear, anxiety, and stress will in turn help to alleviate pain on a different level. Here are a few examples of programs: Low-­Stress Handling Certification: This is an online based (RACE) approved collection

of courses based on the teachings and philosophies of the late Dr. Sophia Yin and covers everything from handling large dogs and how to move them from place to place, and even how to restrain them in a low-­stress manner to allow medical procedures. There are courses on feline socialization, shelter medicine considerations, and even handling and training hyperactive dogs. https://cattledogpublishing.com/ Cat- Friendly Certificate Program: This online program from the American Association of Feline Practitioners (AAFP) consists of nine video-­based modules. This certification program will help the veterinary team understand the needs of cats and develop a feline-­friendly practice. These courses are intended for everyone on the veterinary team from the front office staff to veterinary technicians, and veterinarians. The entire feline visit is described starting with how the waiting room is set up to how the cat is handled during the examination to when the cat is leaving the practice. The AAFP certificate program is a one-­time enrollment fee and does not need to be renewed annually. www.catvets.com Fear Free Certification: Fear Free is a RACE-­ approved certification program that involves online modules and exams to earn the designation of Fear Free Certified Professional (FFCP) covering everything from having a fear-­free exam room to creating fear-­free procedures. The program even covers the pharmacology of sedation, analgesia, and anesthesia medications. Earning the designation of FFCP means you have an annual membership to the program, which requires annual renewal and completion of annual CE to maintain the FFCP designation. www.fearfreepets.com

2.2.15  Veterinary Anaesthesia and Analgesia (MSc), (PgDip), (PgCert), or (PgProfDev) The University of Edinburgh offers a unique opportunity for an entirely online program in  which students can gain knowledge and

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understanding of the equipment, drugs, and techniques associated with anesthesia and analgesia. The program is taught part-­time over 3 years, but its flexible nature will allow you a maximum of 6 years to complete it. There are also options for studying for a certificate (1–2 years) or a diploma (2–4 years). Each year will consist of three 11-­week terms, structured into two blocks of 5 weeks of study, with a week in between for independent study and reflection. The Postgraduate Certificate (PgCert) year (Year 1) starts with a series of compulsory courses to give a foundation in veterinary anesthesia and analgesia, then progresses to examine how this may be applied in a variety of species. In the Postgraduate Diploma (PgDip) year (Year 2), one has the choice of selected courses to tailor the program. A dissertation completes the final year. The Postgraduate Professional Development (PPD) option is for those not looking for credentials, while the master’s program requires a dissertation. www.ed.ac.uk/studying/postgraduate/ degrees/index.php?id=914&r=site/view

2.2.16  Canine Arthritis Management Practitioner (CAMP) The Canine Arthritis Management Practitioner (CAMP) program is a comprehensive overview of canine osteoarthritis (OA) and its evidence-­ based management. Students will learn about all aspects of canine arthritis management, from identification and diagnosis of the disease to evidence-­based multimodal management and end-­of-­life care. Despite being classed as a welfare concern and recognized as one of the leading causes of elective euthanasia, OA is an often overlooked and poorly managed disease. www.ncsuvetce.com/canine-­a rthritis-­ management-­practitioner

2.2.17  Certified Companion Animal Rehabilitation Therapist (CCAT) The CCAT program is a university-­based, RACE­approved credential program for canine

rehabilitation education and training. Deve­ loped using the same strict guidelines typically associated with university-­accredited programs, the CCAT program is taught by a faculty that includes active university instructors, expert clinicians, researchers, and recognized industry experts. The CCAT program draws from ongoing research, hands-­on training, evidence-­ based case studies, clinical experience, and leading companies in the field of veterinary medicine. The CCAT program provides a comprehensive training program on the art and science of canine rehabilitation through a hybrid model of online lecture material and live ­hands-­on training. Students are taught the most up-­to-­date information, train on cutting-­edge modalities, and learn the latest techniques in canine rehabilitation. The high standards and challenging curriculum assure graduates that the CCAT credential is recognized as the premiere program in canine rehabilitation training. Upon successful completion of the CCAT curriculum, the graduate will be able to implement an appropriate rehabilitation protocol for the canine patient. www.ncsuvetce.com/canine-­rehab-­ccat

2.3 ­Leveraging Veterinary Technicians in Pain Management Regardless of the type of practice, veterinary technicians and veterinarians must communicate on a continuous basis about patient care. A veterinary technician may observe a patient’s behavior post-­op that indicates pain and should be able to communicate objective data to the veterinarian so that a change in dosage or drugs can be initiated. But what about other areas where veterinary technicians can be leveraged, especially for those who have advanced training or knowledge? In a veterinarian-­led team, a veterinary technician can be utilized as an intermediary practitioner to manage cases. What does this look like in practice?

2.4 ­Conclusio

After a veterinary-­client-­patient-­relationship, or whatever legal definition is used that establishes a new patient with a veterinarian is satisfied, the veterinary technician can be used to assess and more closely follow up on cases, particularly chronic pain or palliative care patients, by gathering information about the patient’s status, monitoring current medications, supplements or therapies, and working collaboratively with the veterinarian to suggest new modalities or edits to the current treatment plan. In this scenario, the veterinary technician might do rechecks to assess the animal in person or via video telehealth appointments. Or, for some cases, a veterinary technician could review notes or management journals to assist in case efficiency. Management journals are essentially daily or weekly assessments that should include a pain scoring tool like the Canine Brief Pain Index or Feline Grimace Scale to track the success or failures of a treatment plan. The owner should be instructed to note any other new or changing behaviors, food and water intake patterns, sleep patterns, and engagement assessments such as the animal’s willingness to play or engage with the family or other pets in the home setting. In the acute or surgical arena, veterinary technicians can be used to help formulate multimodal analgesic drug protocols, monitor patients undergoing therapies that require closer monitoring, such as sedation for “pain vacations,” and perform ultrasound-­guided nerve blocks. For practices that offer physical rehabilitation services, it is most practical to allow

qualified veterinary technicians to perform rehabilitation techniques and establish a regular clientele.

2.4 ­Conclusion As the veterinary healthcare landscape undergoes continual transformation, the expanding role and increased utilization of veterinary technicians contribute significantly to the evolving paradigm of comprehensive patient care. This evolution presents new and compelling opportunities for the nursing staff to assume pivotal roles within the domain of pain management. In the preface, Nancy underscores a key observation: Veterinarians often rely on technicians as ­primary informants regarding patient pain. Veterinary technicians and nurses, being intimately familiar with the patient’s history and condition, emerge as a central figure in the healthcare team, second only to the owner or primary caretaker. Leveraging their com­ prehensive training and honed senses, and ­fostering collaborative relationships with veterinarians, veterinary technicians are ­optimally positioned to make substantial contributions to the nuanced and multifaceted task of treating animal pain. This collaborative synergy is integral to the advancement and sustained progress of veterinary healthcare, ensuring that our collective impact on alleviating ­animal suffering continues to reach unprecedented heights.

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3 Pain Physiology and Psychology Stephen Niño Cital1,2,4, Tasha McNerney2,3, and Robin Saar 5 1 

Howard Hughes Medical Institute at Stanford University, Stanford, CA, USA Veterinary Anesthesia Nerds, LLC., Sheridan, WY, USA 3  Mt. Laurel Animal Hospital, Mt. Laurel, NJ, USA 4  Remedy Veterinary Specialists, San Francisco, CA, USA 5  Royal Canin Canada, Lethbridge, Alberta, Canada. 2 

3.1 ­Introduction Understanding the physiological and psychological processes by which pain is experienced is an advantage one should invest time and energy into. While it is complex, a little confusing, and ever evolving, having a foundation will better us as practitioners. This foundation, coupled with a strong foundation in pharmacology, will allow us to more precisely formulate an analgesic protocol based on the type of pain, its origins and potential psychological effects that the pain experience brings. In this chapter we offer that foundation of pain physiology and the psychological aspects surrounding the pain experience.

3.2 ­What Is “Pain” First and foremost, pain is a subjective emotion experienced differently by every individual. Pain can be experienced in the absence of an obvious cause and can be malleable based on various other experiences such as memory, fear, or anxiety. Throughout this book we will use the term pain to refer to clinical symptoms that are associated with trauma or a disease process that

are causing physical discomfort to an animal. However, we encourage readers to be aware of the nuances with the term, which can extend beyond the physical to include the psychological and even the expansion of certain types of pain being considered as not just an emotional experience but a legitimate ­disease itself (Treede et al. 2019; Raffaeli and Arnaudo 2017). Physiological pain, rather nociceptive processing, is hardwired into all living organisms as an alarm system, a defense mechanism we all share to put us out of harm’s way. Sensory nerve fibers all along the body called nociceptors have the incredible ability to detect a huge range of stimuli such as temperature, pressure, and vibration, and determine whether these are innocuous or noxious, and a potential physical threat. The updated International Association for the Study of Pain (IASP) defines pain as “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” The IASP also acknowledges that the “inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain.” Within this statement, it is critical to note that in the case of veterinary patients compared to

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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our human counterparts, the inability to communicate verbally does not negate the possibility that an individual is experiencing pain and needs appropriate pain-­relieving treatment. Two definitional approaches have been used to address pain in nonverbal creatures. One is to accept definitions that emphasize a conscious experience, such as the IASP definition, and to argue based on sufficient neuroanatomical, physiological/pharmacological, and behavioral analogies that certain species are likely to experience pain similarly to humans – while admitting that compelling proof of the existence of conscious pain in other species may be impossible. This approach has profound ethical and legal implications, as persuasive evidence for conscious pain – and thus for potential suffering – is the basis for including any species for protection under animal welfare laws and holding ourselves as practitioners to an ethical standard of providing some level of intervention. Another approach is to define pain based on functional rather than subjective properties. For example, researchers studying injury-­ induced sensitization of defensive behavior in Drosophila larvae (a species of fruit fly), which was a rolling behavior when touched with a hot needle, assume the functions of such sensitization are the same as for mammalian allodynia and hyperalgesia (types of conscious evoked pain as defined by the IASP) and use these terms (and sometimes the word pain) to refer to injury-­related states in this insect – without explicitly arguing that flies might have a conscious pain experience (Elwood  2019). Pain’s pathophysiological and psychological toll is also highly nuanced given the species neurological/ cerebral development, sex, and specific adaptations various animals may have acquired in evolution or even domestication.

3.2.1  The Negative Effects of Pain ●●

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Pain produces a catabolic state (energy release), which may lead to wasting. Pain suppresses the immune response, ­predisposing to infection or sepsis and increasing hospitalization time and cost.

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Pain promotes inflammation, which delays wound healing. Anesthetic risk is increased because higher doses of anesthetic drugs are required to maintain a stable plane of anesthesia. Pain causes patient suffering, which is also stressful for owners and caregivers.

3.3 ­Breaking Down the Nociceptive Pathway The physiology of the nociceptive pain pathway is based on the body’s ability to self-­preserve. Generally speaking, and in short, a noxious stimulus  – think of a scalpel blade cutting the skin – are transduced with the initial signal, then transmitted to the dorsal horn of the spinal cord where it is then modulated. After modulation, the signal travels to the brain to be perceived as a  noxious stimulus with an affect known ­commonly as pain (Gaskin et  al.  1992; Yam et  al.  2018). This whole experience along the pathway is termed nociception and allows the body to initiate protective reflexes  – usually a physical movement – in response to the stimuli.

3.3.1  Transduction Nociceptors play a crucial role in the detection and transmission of pain signals in animals. These specialized sensory nerve fibers, also known as primary afferents, are the first to receive information about potential damage to tissues, whether due to injury, surgery, or other causes. Their role is to convey this  information toward the central nervous system. Located throughout the body, these nerve fibers are key initiators in the pain detection process. They are responsible for identifying and processing harmful or potentially harmful stimuli. The activation of these nociceptors occurs once a certain pain threshold is reached, which is the minimum level of stimulus needed to trigger a response from the ­nervous system.

3.3 ­Braaing oon hr  ocicre iirPa hoay

At the site of injury, primary afferent terminals serve as transducers. They transform ­various forms of energy – be it chemical, mechanical, or thermal – into electrical signals that the nervous system can interpret. These signals then travel along the afferent nerve ­fibers to the spinal cord’s dorsal horn and ­subsequently to the brain. The types of stimuli that can lead to pain perception are diverse. Specialized receptors in these nociceptors are tuned to detect thermal, chemical, or mechanical changes related to

different kinds of injuries. For instance, thermoreceptors react to extreme temperatures, chemical nociceptors respond to both internal biochemical changes from damaged cells and external substances like capsaicin or menthol, and mechanoreceptors are sensitive to physical changes such as pressure, swelling, or cuts. When tissues are significantly damaged, a variety of chemicals are released in the vicinity of the injury, creating an acidic “inflammatory soup” (Figure  3.1). This mixture serves to

Perception

Modulation

Transmission

Transduction

Transmission Inflammatory Soup Noxious Stimuli

Leukotrienes

Bradykinin

Nocioception Prostaglandin

Arachidonic Acid

Transduction

Glutamate Histamine

Substance P Mast Cell

Serotonin

Cytokines

Tissue Damage

Figure 3.1  The pain pathway with inflammatory soup. Source: Drawn by Mark Brinker.

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stimulate and sensitize the nociceptors, leading to a state of hyperalgesia or increased sensitivity, as a protective measure against further harm. Key components of this inflammatory soup include substances like bradykinin, ­serotonin, histamine, cytokines, interleukins, arachidonic acid, prostaglandins, leukotrienes, hydrogen ions, substance P, and glutamate. Each of these plays a role in amplifying the pain signal and the body’s response to injury (Yam et al. 2018).

3.3.2  Transmission In the process of pain perception, specialized nerve endings transform detected, via transduction, information into electrical impulses known as action potentials. These nerve endings, varying in sensitivity, have specific thresholds required to trigger these electrical signals. The nerve fibers involved in this ­process are categorized as A-­delta, A-­beta, or C fibers. A-­delta and C fibers are  primarily involved in pain sensation (nociception), while A-­beta fibers convey nonpainful information. Low-­threshold A-­beta receptors, located in skin, muscles, and joints, are sensitive to touch, vibration, movement, proprioception, and pressure. On the other hand, high-­ threshold A-­delta nociceptors are smaller nerve fibers sheathed in myelin, an insulating fatty substance that accelerates impulse transmission. These A-­delta receptors react to thermal or mechanical stimuli and are associated with sharp, acute pain, often described as the “first pain” experienced immediately after injury. Conversely, “second pain” is transmitted via smaller, unmyelinated C-­fibers. These polymodal fibers respond to mechanical, thermal, and chemical stimuli. Their slower conduction velocity leads to a less localized, burning pain often linked with ongoing tissue damage and inflammation. C-­fibers also play a significant role in the development and maintenance of chronic pain.

The transmission of pain signals begins at the injury site and progresses to the dorsal horn of the spinal cord. From there, the signals move to the brainstem and then along sensory pathways to the brain. Both A-­delta and C-­fibers terminate in the spinal cord’s dorsal horn, where they encounter a synaptic cleft. To bridge this gap and continue their journey to the brain, neurotransmitters like norepinephrine and serotonin are released, facilitating the transmission of the pain signal (Yam et al. 2018).

3.3.3  Modulation Pain modulation refers to the alteration, suppression, or enhancement of impulse transmission within the spinal cord. The spinal cord itself is composed of distinct areas: the nerve cells form the gray matter, while the axons of nerve fibers constitute the white matter. The gray matter is further divided into three distinct regions: the dorsal horn, the ventral horn, and the intermediate zone, each playing a role in the processing and transmission of neural signals (Yam et al. 2018).

3.3.4  Perception Pain perception is a complex and dynamic conscious experience that involves recognizing and interpreting sensory inputs. At the core of this process is the somatosensory ­cortex, a region of the cerebrum that plays a crucial role in the advanced processing and conscious awareness of pain. This area of the brain integrates and interprets sensory information received from various parts of the body, enabling individuals to perceive and understand the nature and intensity of pain. The somatosensory cortex, along with other areas of the brain such as the thalamus and limbic system, contributes to the multidimensional experience of pain. These areas work together to analyze the pain’s location, intensity, and quality, and to associate it with emotional responses and memory. This integrative approach allows the brain to not

3.3 ­Braaing oon hr  ocicre iirPa hoay

only perceive pain but also to evaluate its potential threat and prioritize responses in real time and in the future (Sgourdou 2022). Pain perception is not just a simple response to a stimulus, but a multifaceted experience influenced by a range of factors, including emotional and cognitive states. The brain’s interpretation of pain signals can vary significantly depending on context, previous experiences, expectations, and even cultural factors  – yes animals have their own forms of culture (Laland and Hoppitt  2003). For instance, the same injury might be perceived differently by different ­animals or even by the same individual under different circumstances. Furthermore, the somatosensory cortex is involved in differentiating between various types of pain, such as sharp versus dull pain or acute versus chronic pain. This differentiation is crucial for appropriate pain management and response, especially in cases of chronic pain where the pain perception process might be altered.

Peripheral nerve

3.3.5  The Dorsal Horn The processing of sensory information within the spinal cord primarily occurs in the dorsal horn. This region acts as a hub, receiving sensory inputs and relaying them to the brain for advanced processing. The dorsal horn comprises a network of interneurons and ascending pathways that facilitate the transmission of this information (Figures 3.2 to 3.4). These interneurons can be either excitatory, enhancing signal transmission, or inhibitory, dampening it, and are crucial for local signal modulation. Sensory data arriving at the dorsal horn is transferred across the synaptic cleft – the gap between adjacent neurons  – and then conveyed to the brain. This triggers the activation of descending control systems, which adjust the dorsal horn’s responsiveness to both ­excitatory and inhibitory signals. Various neurotransmitters play a pivotal role in transmitting information from peripheral areas to

Dorsal root ganglion

Aβ

A∂ Sympathetic ganglion

Spinal cord

C-fibers

Figure 3.2  Low-­threshold A-­beta nerve fibers; high-­threshold, myelinated A-­delta fibers; and small, unmyelinated C fibers lie within the peripheral nerve sheath and synapse in the dorsal horn of the spinal cord. Source: Drawn by Mark Brinker.

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Superficial dorsal horn C-fiber

I

• Primary afferent nociceptor • High threshold • Small, thin, unmyelinated • Slow, dull, chronic pain

A-delta fiber

II

• Primary afferent nociceptor • High threshold • Small and myelinated • Fast, sharp, acute pain

0

su

i

III/

IV

ma

bs

II

rg

tan

tia

ge

nu

lat

cle

us

pr

op

ina

ino

l la

ye

r

sa

riu

s

A-beta • Sensory nerve fiber • Low threshold • Large diameter, myelinated • Innocuous sensations

Figure 3.3  A-­delta, A-­beta and C fiber synapse within the superficial laminae of the dorsal horn of the spinal cord. Source: Drawn by Mark Brinker.

Pain

Ascending Pathway Primary somatosensory cortex

Thalamus

Medulla oblongata (brain stem)

Spinothalamic tract A-delta and C-fiber Primary afferent nocioceptors

Dorsal horn

Intermediate zone Ventral horn

Reflex pathway

Figure 3.4  A-­delta and C fibers enter the dorsal horn of the spinal cord. Here, the impulse can generate a reflexive response by following the reflexive pathway or be sent up to the brain for further processing. The spinothalamic tract travels through the medulla, to the thalamus, and then on to the somatosensory cortex where it can be perceived as pain. Source: Drawn by

3.3 ­Braaing oon hr  ocicre iirPa hoay

spinal cord neurons. Key neurotransmitters include substance P, glutamate (an excitatory neurotransmitter), gamma-­aminobutyric acid (GABA – the primary inhibitory neurotransmitter in the mammalian central nervous system), endogenous opioids, and monoamines like serotonin and norepinephrine. These neurotransmitters interact with specific receptors to either amplify or dampen incoming signals. For instance, glutamate may intensify pain signals, while GABA tends to suppress them. Serotonin and norepinephrine can modulate these effects by inhibiting excitatory neurotransmitters like glutamate or supporting inhibitory ones like GABA, thus influencing the pain signal intensity enroute to the brain. Behind the scenes the endocannabinoid system (ECS) is actively trying to maintain systemic homeostatic and informing other physiological systems of the potential threat. The dorsal horn’s architecture is organized into clusters of neurons grouped by function and is further divided into 10 strata known as Rexed laminae. Sensory nerve fibers relay information to these various laminae, where substances such as glutamate and peptides like substance P activate diverse postsynaptic receptors. The first two laminae, Laminae I and II, are primarily involved in processing nociceptive (pain-­related) inputs and are collectively referred to as the superficial dorsal horn, with Lamina I known as the marginal layer and Lamina II as the substantia gelatinosa.

3.3.6  Ventral Horn and  Intermediate Zone The ventral horn in the spinal cord is composed of interneurons and primarily concerns itself with controlling motor functions and skeletal muscle activities, as opposed to processing sensory data. Meanwhile, the intermediate zone of the spinal cord is situated between the dorsal and ventral sections of the gray matter, which is butterfly shaped. This region plays a pivotal role in managing

impulses that regulate visceral functions and in relaying information to more advanced neural centers.

3.3.7  White Matter White matter in the spinal cord is segmented into three key regions: dorsal, ventral, and lateral columns. Each of these areas is composed of axons that facilitate the transfer of information between the brain and other parts of the body. The dorsal column primarily handles the transmission of somatic sensory data to the medulla. In contrast, the ventral column is responsible for conducting signals from the brain to the skeletal muscles. The lateral column plays a role in conveying somatic sensory information to the brain and encompasses nerve fibers associated with sensory, motor, and autonomic functions.

3.3.8  Descending Pathways The modulation of pain sensations occurs as they ascend to the brain through pathways in the dorsal horn. Concurrently, descending pathways regulate pain by transmitting signals from the brain’s higher centers. These controlling pathways originate from the cortex, thalamus, and brainstem. The mechanism of descending inhibition involves relay stations located in the brainstem, which employ neurotransmitters such as serotonin and norepinephrine, along with endogenous opioids, to assist in the suppression of pain.

3.3.9  Spinothalamic Tract Within the spinal cord, neurons in the dorsal horn transmit pain signals upward through the white matter via the spinothalamic tract. This tract, an essential ascending nociceptive pathway, conveys information about actual or potential tissue damage toward the brain. Its roots lie in the dorsal horn, and its primary function is to carry information about superficial pain and tactile sensations, such as touch. In carnivores, the spinothalamic tract is

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recognized as a key pathway for conscious pain perception. From the dorsal horn, the tract’s projections extend through the brainstem, reaching the thalamus. Subsequently, these signals are relayed to the somatosensory cortex in the brain. This pathway plays a vital role in the processing and perception of pain, forming a crucial part of the neural mechanism that allows organisms to react to and manage painful stimuli.

3.3.10  Spinoreticular Tract Sensory signals from visceral organs and deeper bodily tissues are transmitted via the spinoreticular tract. Unlike other pain pathways, most of these neural projections do not pass through the thalamus but instead terminate in the reticular formation, located within the brainstem. This area is crucial for screening incoming sensory stimuli and plays a key role in regulating vital functions such as heart rate and respiratory rate. It is also involved in maintaining cortical alertness and consciousness. Within the reticular formation, pain stimuli can evoke an emotional response by activating the limbic system. This system encompasses various brain structures that govern emotions, behavior, sense of smell, and memory. The nature of the spinoreticular pathway, being more dispersed, often results in the pain processed here being less precisely localized. The involvement of the limbic system highlights the complex interplay between physical sensations of pain and their emotional and psychological impacts.

3.3.11  Peripheral Sensitization Peripheral sensitization is a reduction in threshold and an increase in the responsiveness of peripheral nociceptors. Normally, high-­ threshold nociceptors A-­delta and C fibers are activated in response to noxious stimuli. Damaged cells release chemical mediators in

response to tissue injury and inflammation. These substances have direct effects on the excitability and sensitizing of sensory nerve fibers. They promote vasodilation and recruit inflammatory cells, macrophages, lymphocytes, platelets, as well as the substances implicated in the inflammatory soup. This effectively lowers the response threshold for A-­delta and C fiber activation. Silent nociceptors are exquisitely sensitive to the effects of inflammatory soup and go from benign unmyelinated polymodal C fibers to vigorously firing C fibers (Table 3.1; Muir 2009).

3.3.12  Central Sensitization Central sensitization is contingent on the development of peripheral sensitization and is  the indirect consequence of tissue trauma and inflammation. Sensations of pain spread beyond the site of insult to nearby undamaged tissue. Central sensitization can result from unrelenting stimulation to the peripheral nociceptors, which leads to the sustained release of glutamate and other neurotransmitters from primary afferent nerves (Figure 3.5). The liberation of these substances activates dorsal horn receptors like 2-­amino-­3-­(3-­hydroxy-­ 5-­methyl-­isoxazol-­4-­yl) propanoic acid (AMPA) and N-­methyl-­d-­Aspartate (NMDA), which will then lead to an increase in the excitability of the dorsal horn neurons projecting up to the brain (Lamont et  al.  2000; Muir  2009). This “windup” of the CNS is the inciting cause of central sensitization, exaggerating subsequent nociceptive and non-­nociceptive input. Windup itself is a term often used interchangeably and incorrectly with central sensitization. However, windup can be a precursor to central sensitization referring to the progressive increase of C-­fiber evoked responses via the dorsal horn from repetitive activation (Li et al. 1999). For central sensitization the AMPA and the NMDA receptors are both activated by glutamate, but each has its own distinct properties. Noxious stimulation causes a release of

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Table 3.1  Common inflammatory mediators of pain (Muir 2009: Mosley et al. 2021). Mediator

Origin

Action

Adenosine Triphosphate

Damaged tissue

ATP is metabolized into adenosine by ectonucleotidases and binds to its receptor, ionotropic purine receptors (P2X) that are located at the peripheral site of the sensory neurons and centrally on the second-­order neurons in the dorsal horn. In general, there are six types of P2X receptors. Of these six types, purine receptor type 3 (P2X3) receptors are one of the most selectively expressed receptors in the small C-­fiber nociceptor. Once the ATP binds to the P2X3 receptors, Na+ can cross these channels and induce membrane depolarization, hence activating various Ca2+-­ sensitive intracellular processes and causing both pain and hyperalgesia.

Arachidonic acid

Damaged tissue

Mediators and regulators of inflammation as well as the actions of prostaglandins (platelet aggregation, blood clotting, smooth muscle contraction, immune function, etc.).

Bradykinin

Damaged tissue

Inflammatory chemicals implicated in the production of other chemicals like histamines and prostaglandins. Bradykinin has been shown to produce pain by attaching to nociceptors and initiating CNS impulses.

Cytokines

Released from cells during inflammation

Cytokines may excite nociceptors by stimulating the release of other mediators like prostaglandins. May play a role in hyperalgesia.

Endocannabin-­oids

Endocannabinoid system (ECS)

Endocannabinoids can bind to G-­protein coupled cannabinoid type 1 receptors (CB1), which is highly expressed in the pre-­and postsynaptic brain and spinal cord, as well as the G-­protein-­coupled cannabinoid type 2 receptors (CB2) that is predominantly located in the immune system. The activation of CB1 and CB2 inhibits the formation of intracellular cAMP, hence leading to a tremendous reduction of the excitatory effect within the neurons.

Glutamate

Damaged tissue

Excitatory neurotransmitter used by all primary afferent nerves to elicit fast, excitatory responses to noxious stimuli.

γ-­Aminobutyric acid (GABA)

Produced by GABAergic neurons, which are concentrated in the brain

Most widely distributed inhibitory transmitter in a mammalian CNS. When GABA binds to GABAA receptors, there is an inflow of extracellular Cl− into the neurons, thus reducing the membrane potential and resulting in an inhibitory effect. On the other hand, the binding of GABA to GABAB receptors causes an inhibition toward the formation of cAMP, because the GABAB receptor is a Gi-­protein-­coupled receptor. (Continued )

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Table 3.1  (Continued) Mediator

Origin

Action

Histamine

Mast cells

Inflammatory mediator causes vasodilation and edema, enhances the response to bradykinin and heat, and excites polymodal visceral nociceptors. Also plays a role in the response to allergens and causes itching

Interleukins

Generated during acute inflammation

A type of cytokine that can cause fever and initiate prostaglandin production and stimulate the secretion of ACTH and cortisol.

Leukotrienes

Derived from arachidonic acid

Arachidonic acid metabolite that mediates inflammation and promotes GI mucosa damage and pain

Nerve growth factor (NGF)

Locally released at the site of injury by fibroblasts

NGF is expressed rapidly and can induce a rapid onset of mechanical and thermal hyperalgesia. NGF-­dependent nerve fibers, known as tropomyosin receptor kinase A (TrkA), are also a high-­affinity NGF receptor. This receptor is widely expressed in the primary afferent neurons with up to 50% coverage which suggests its direct role in activation for peripheral sensitization.

Prostaglandins

Derived from arachidonic acid and released from damaged cells

Both homeostatic and pathogenic functions including generation of the inflammatory response, which contributes to the signs associated with inflammation, pain, redness, swelling, and heat

Serotonin

Degranulated mast cells in the peripheral tissues

Excitatory neurotransmitter that can potentiate the pain caused by bradykinin. Serotonin has the potential to modulate pain in the dorsal horn.

Substance P

Damaged tissue

Neurotransmitter that transmits pain impulses from the peripheral nervous system (PNS) to CNS

Presynaptic neuron

Presynaptic neuron

Glutamate Magnesium (Mg2+) Sodium (Na+) Na+

Calcium (Ca2+)

Na+

Mg2+ AMPA receptor

NMDA receptor Na+ Postsynaptic neuron

Ca2+

Na+

Mg2+

AMPA receptor

NMDA receptor Na+

Ca2+

Na+

Postsynaptic neuron

Figure 3.5  Noxious stimulation causes a release of glutamate, which binds to both AMPA and NMDA receptors. Weak stimulation only activates the AMPA receptor to generate action potentials. The NMDA receptor is normally blocked by Mg2+, not allowing ions to freely pass through to generate an impulse. During significant stimulation, the AMPA receptor can depolarize the membrane with the strength to dislodge the Mg2+ from the NMDA receptor, allowing it to respond to glutamate. Once activated, the NMDA receptor allows large amounts of Ca2+ to pass through, activating several intracellular cascades leading to heightened nerve excitability (Woolf and Salter 2006). Source: Drawn by Mark Brinker.

3.4 ­hr ndocannaainoid ys re and Pain

glutamate, which binds to both AMPA and NMDA receptors. Weak stimulation activates only the AMPA receptor, resulting in slight cell depolarization by making the postsynaptic neuron permeable to Na+ and K+ (to generate action potentials). The NMDA receptor is normally blocked by Mg2+ so it doesn’t allow ions to freely pass through to generate an impulse. During weak stimulation, excitatory signals are mediated entirely by the AMPA receptors. When greater stimulation occurs, AMPA receptors can depolarize the membrane with the strength to dislodge the Mg2+ from the NMDA receptor, allowing it to actively respond to glutamate. When activated, the NMDA receptor allows large amounts of Ca2+ to pass through, activating several intracellular signaling cascades and ultimately leading to increased nerve transmission and heightened nerve excitability (Woolf and Salter 2006).

3.4 ­The Endocannabinoid System and Pain The ECS is a physiological system that is gaining much more attention in both human and veterinary medicine since its discovery in 1988. The ECS is not fully understood, but what researchers do know is that it plays a crucial role in the entire spectrum of pain’s pathophysiological processes. It is significantly involved in every stage of the nociceptive ­pathway, which includes transduction, transmission, modulation, and perception of pain, impacting both the incoming and outgoing ­signals related to pain. The ECS exerts its influence across key points in the pain pathway, including peripheral areas, the spinal cord, the periaqueductal gray matter (PAG), and the ventroposterolateral nucleus of the thalamus. This ECS is composed of endocannabinoids (cannabinoids produced by the body), catalyzing and hydrolyzing enzymes, endocannabinoid like compounds, and two primary cannabinoid receptors, CB1 and CB2.

Additionally, the endocannabinoids and enzymes within the ECS are known to interact with and modulate traditional receptors involved in pain signaling such as opioid receptors, NMDA receptors, GRP55 receptors, and glycine receptors, among others. Certain hormones, including oxytocin, have been found to influence the release and effects of endocannabinoids like anandamide. Any imbalance or malfunction in the components of the ECS, often referred to as the endocannabinoidome, can result in pathological pain. The CB1 receptor has a significant role both centrally and peripherally, operating through direct and indirect mechanisms. These receptors are predominantly located pre-­synaptically within the nervous system and regulate synaptic transmission by controlling the release of specific neurotransmitters and neuropeptides based on physiological requirements and triggers. The analgesic effects of the ECS are attributed to its ability to inhibit nociceptive transmission, acting as a kind of “retrograde synaptic circuit breaker.” CB1 receptors are strategically positioned at various pain signaling synapses, including at the peripheral and terminal ends of primary afferent neurons, in the dorsal root ganglion (DRG), the dorsal horn of the spinal cord, the PAG, the ventral posterolateral thalamus, and cortical regions. Essentially, these receptors can block any neurotransmitter released across a synapse that could facilitate pain transmission between neurons. Research on the ECS has primarily focused on two endocannabinoids, anandamide (AEA) and 2-­Arachidonoylglycerol (2-­AG), though other endocannabinoids are also recognized. More recent studies have identified additional CB1-­interacting peptides and a range of arachidonic acid derivatives that produce effects like endocannabinoids. The modulation of pain by the ECS occurs at multiple levels, including peripheral, spinal, and supraspinal, underscoring its crucial role in both the ascending and descending pathways of pain processing. This system’s influence extends

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across various stages of pain management. Endocannabinoids are released in response to conditions such as tissue damage, inflammation, or abnormal pain signaling. Their primary function is to reduce pain sensitivity and mitigate the progression of inflammatory responses. This action of endocannabinoids represents a key aspect of pain management mechanisms. Anandamide, an endocannabinoid, acts as a partial agonist with strong affinity for CB1 receptors, leading to the inhibition of neurotransmitter release. While initially thought to be inactive on CB2 receptors, recent research indicates its role in alleviating certain types of neuroinflammation, as observed in rat microglial cell cultures. As a full agonist of the transient receptor potential vanilloid 1 (TRPV1) channel and active on other G-­protein-­coupled receptors like GPR18 and GPR55, anandamide triggers desensitization and depolarization. This action results in the inactivation of voltage-­ dependent sodium and calcium channels, reducing neuron firing and thus contributing to  pain relief and decreased hypersensitivity. Anandamide is also referred to as an “­endovanilloid” due to its activation of the TRPV1 receptor. Anandamide shares a similar action mechanism to gabapentin in inhibiting T-­voltage gated calcium channels, often upregulated in chronic pain states. Its other analgesic effects include inhibiting 5-­HT3A serotonin receptors, activating peroxisome proliferator-­ activated receptors (PPARs), and enhancing the function of glycine receptors. 2-­AG, another and most common endocannabinoid, acts as a full agonist on both CB1 and CB2 cannabinoid receptors, with low to moderate affinity for CB1 and high affinity for CB2 receptors. Its pain-­relieving mechanisms also involve potentiating the GABA receptor and affecting PPAR-­γ receptors, which helps in reducing neuronal excitability and inflammatory responses. Furthermore, 2-­AG’s interaction with endogenous norepinephrine can activate peripheral adrenoceptors, contributing to its analgesic effects (Mosley et al. 2021).

3.5 ­The Gate Control Theory The gate control theory, introduced in 1965, provides a foundational understanding of pain modulation and offers an insight into why instinctive reactions like rubbing or applying pressure to an injured area can help lessen pain. According to this theory, engaging in actions such as rubbing, shaking, or pressing on a painful area stimulates larger, low-­ threshold A-­beta receptors. This stimulation leads to an enhanced inhibitory action of interneurons, which in turn lowers the transmission of pain signals. These A-­beta receptors, when activated, increase the inhibitory effects on A-­delta and C-­fiber nociceptive neurons, which are responsible for transmitting pain signals. This is conceptualized as closing a metaphorical “gate” in the spinal cord’s neurological pathways. When this gate is closed, the transmission of pain signals to the brain is impeded, effectively dampening the pain sensation. Expanding on this, the gate control theory signifies a shift in understanding pain from a purely physical or linear process to one that involves complex interactions within the nervous system. It acknowledges that pain perception isn’t just a direct result of injury or tissue damage but is also significantly influenced by both psychological and physiological factors. This theory underscores the role of the brain and spinal cord in pain perception, suggesting that pain signals can be modulated or altered as they pass through various neural “gates” at the spinal level before reaching the brain. It highlights the interplay between different types of nerve fibers and how their interactions can either amplify or dampen pain signals. Moreover, the gate control theory has implications for pain management, suggesting that nonpharmacological interventions like massage, acupuncture, and even certain psychological strategies can effectively alter pain perception. This understanding has paved the way for more holistic approaches in pain ­management, integrating both physical and psychological strategies (Muir 2009).

3.6 Psychological serc soo Pain

3.6 ­Psychological Aspects of Pain 3.6.1  Personality and the Pain Experience The concept of animal personalities, once largely ignored in scientific circles, has recently gained recognition for its potential to enhance the management and welfare of captive animals. Ensuring proper animal welfare, particularly in veterinary practices, involves the vigilant monitoring and management of pain. This process depends on observing various behavioral and physiological signs. Notably, distinct physiological traits or coping mechanisms can influence consistent behavioral ­variations, often termed as “personality.” Such personality traits could potentially influence the accuracy of pain assessments. Studies in dogs, cats, and horses have provided preliminary clues on how an animal’s personality may affect their pain experience and should be considered when assessing pain in animals. See Chapter  4 for more on this topic (Lush and  Ijichi  2018; Litchfield et  al.  2017; Ijichi et al. 2014).

3.6.2  Stress and Anxiety on Pain Pain, much like stress, can have detrimental effects on health. Experiencing pain is inherently stressful, primarily due to the biological responses it triggers in the brain, particularly in the hypothalamus. The hypothalamus serves a central role in coordinating autonomic responses and integrating both physiological and emotional reactions in the body. When activated by pain, it stimulates the sympathetic nervous system, often referred to as the “fight-­ or-­flight” response and influences the pituitary gland. This activation leads to an increased release of adrenaline (epinephrine and norepinephrine) and glucocorticoids, which are key components of the body’s stress response (Hekman et al. 2014). The relationship between stress and pain is bidirectional and complex. Stress can amplify the perception of pain, just as pain can

exacerbate stress. A common example can be seen in animals, such as a cat experiencing heightened stress while confined in a crate in a noisy clinic, where both the environment and the physical discomfort intensify the animal’s stress and perception of pain. In human medicine, the interplay between emotional state and pain perception is well-­ documented. Individuals with chronic pain often show higher rates of depression, and conversely, those suffering from depression frequently report increased pain sensitivity. This intertwining of depression and chronic pain is often referred to as the depression-­pain syndrome or the depression-­pain dyad. This syndrome underscores the importance of considering both psychological and physical aspects in pain management. Psychogenic stress due to hospitalization, sometimes referred to as “hospital psychosis,” is also a phenomenon that has only recently started being described in animals. The mere displacement of the animal from its home environment can add to the stress/anxiety an animal experiences, thus impacting pain states. Treating pain is not just about addressing the physical symptoms but also involves managing the psychological impacts, highlighting the need for a holistic approach to pain management in both human and veterinary medicine. Pain management protocols should include stress or anxiety assessments and, where appropriate, anxiolytic medications (Abdallah and Geha 2017; Hekman et al. 2014).

3.6.3  Pain Catastrophizing The term pain catastrophizing in the clinical context traces its roots back to Albert Ellis, who first discussed it in his 1962 publication, focusing on the cognitive foundations of emotional disorders. Ellis described catastrophizing as the irrational tendency to anticipate negative future events pessimistically. Subsequently, Aaron Beck and his team defined it as a fixation on the worst possible outcomes in any given situation. This concept

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was later embraced by pain researchers to explain negative pain-­related outcomes, with Sullivan and colleagues defining pain catastrophizing as an excessively negative mindset applied during real or anticipated pain experiences (Sullivan and Tripp  2023; Sturgeon and Zautra 2016). How does this apply to animals? While various definitions of catastrophizing converge on the theme of anticipating negative future outcomes, its conceptualization differs between mental health and pain research. In human mental health, catastrophizing is seen as overestimating the likelihood of negative events, whereas in pain research, it’s viewed as an exaggerated perception of threat from one’s symptoms. More recently, Gellatly and Beck have suggested that catastrophizing may be a maladaptive process. In animals, we may see a convergence of both the psychological and physiological pain. A possible example of pain catastrophizing is with animals receiving nail trims with a severe over reactions to the event. An animal may be calm and collected during the initial restraint, but once the animal sees the nail clippers or has paws manipulated, the animal may vocalize or try to escape from manual restraint. Each subsequent event can escalate the anticipatory pain or perceived discomfort experienced from the previous event (Rasmussen et al. 2023).

3.6.4  Boredom and Pain Boredom, like stress or anxiety, can significantly impact the experience of pain, altering both its perception and intensity. When an animal is bored, its mind lacks stimulation and engagement, which can lead to an increased focus on internal sensations and feelings, including pain. In the absence of distractions or engaging activities, the mind may become more attuned to bodily discomforts that might otherwise go unnoticed or be deemed less ­significant. A heightened awareness due to boredom can make pain feel more intense. Additionally, boredom often leads to a negative

emotional state, including feelings of irritability or sadness, which can further exacerbate the perception of pain. This phenomenon is particularly evident in chronic pain patients, where long periods of inactivity or lack of engaging stimuli can lead to a heightened focus on their pain, contributing to a cycle of discomfort and negative emotions. This is commonly seen when dogs lick a sore joint. In humans, less enriched individuals appear to decompensate quicker, both psychologically and physically. It is not inconceivable to say that animals also may experience a more rapid decline when they have a pain condition and are under-­enriched. Furthermore, boredom can impact the way pain is managed and coped with. Enhanced enrichment activities (puzzle feeders, car rides, new toys) can serve as effective distractions from pain and can also provide a sense of accomplishment or pleasure, which can mitigate pain perception (Bliss-­Moreau 2017). Recent studies have indicated that when placed in a dull, unstimulating laboratory environment, individuals who do not have clinical conditions have shown a tendency to self-­ administer electric shocks. It appears that these shocks provide a break from the tedium of the environment, being the sole external source of stimulation available (Bliss-­Moreau et al. 2018). Another perspective is that these shocks may serve to manage the discomfort caused by boredom, aligning with theories that suggest nonsuicidal self-­injury (NSSI) acts to regulate negative emotions. To explore this idea further, a study involving 69 participants was conducted. These participants were exposed to either a monotonous, saddening, or neutral video clip, during which they had the option to self-­administer electric shocks. The findings revealed that participants in the boredom group administered more shocks to themselves, and at higher intensities, compared to those in the neutral and sadness groups. Interestingly, experiencing sadness did not lead to an increase in shock self-­administration. Notably, individuals with a history of NSSI exhibited a more pronounced response to

3.6 Psychological serc soo Pain

boredom, administering more shocks in the initial 15 minutes. These results suggest that the primary function of these self-­administered shocks is to disrupt the monotony rather than to regulate general negative emotional experiences. The study underscores the significance of boredom as a potential trigger for NSSI behaviors (Nederkoorn et  al.  2016). These types of studies have been performed in both animals and humans with not only physical distractors, like electric shocks, but also substances commonly associated with abuse such as alcohol and cocaine. These studies also suggest a potential etiology for animals that display compulsory behaviors that produce injury, again such as excessive licking, feather plucking in birds, or other self-­injurious behaviors (Mieske et al. 2022).

including the medial prefrontal cortex, thalamus, amygdala, and anterior cingulate cortex (Baliki et al. 2006). These areas are associated with functions such as learning, memory, fear, and emotional responses and map on to cognitive and emotional problems suffered by chronic pain patients, such as elevated anxiety and depression. Patients with a history of significant pain or central sensitization from prolonged pain are harder to treat and are less responsive to analgesic therapy likely due to the formation of these memories and alterations of the nervous system (Song and Carr 1999; Muir 2009). Preemptive analgesia is thought to decrease the emergence of central sensitization and all the negative sequelae associated with it, including nervous system reorganization and the memory of pain (Monteiro et al. 2022).

3.6.5  Neuroplasticity and the Memory of Pain

3.6.6  Caregiver Placebo

Neuroplasticity refers to the ability of neurons to change their structure and function in response to different environmental stimuli. This type of flexibility allows us to navigate our environment and respond to its evolution. In response to trauma, unrelenting pain, or peripheral and central sensitization, the nervous system can reorganize itself and develop new stimulus–response relationships (Muir  2009). The CNS forms memories and relationships that may be beneficial but are more often detrimental. Pain can alter gene expression, and those patients who have a history of injury may be more sensitive to future nociceptive input. How memory affects pain and how pain affects memory depends on the individual’s environment, expectations, and behaviors as well as the intensity of the painful event. The response to subsequent pain is likely to be more severe and disproportionate to the stimulus encountered. Recent work in both human patients and laboratory animals has demonstrated that the presence of chronic neuropathic pain causes gross reorganization and functional changes in both cortical and subcortical structures,

The caregiver placebo effect refers to a phenomenon where caregivers (often pet owners or most often veterinary practitioners) perceive an improvement in a patient’s condition, such as reduced symptoms or better overall health, when the patient has been receiving treatment  – whether that treatment is effective or not. The caregiver placebo effect is particularly notable in clinical trials and medical situations where the effectiveness of a new treatment is being evaluated. In veterinary medicine, for example, a pet owner might report that their animal’s condition has improved after the animal has received a placebo treatment. Similarly, in human medicine, family members or caregivers of a patient might observe and report improvements in the patient’s condition when the patient is receiving a placebo. The caregiver placebo effect is important because it can introduce bias in the assessment of the efficacy of medical treatments. It highlights the subjective nature of observing and reporting changes in a patient’s condition, especially

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when those observations are made by individuals who are emotionally invested in the patient’s recovery. This effect underscores the necessity of objective measurements, such as using pain scoring tools, and blinded studies in clinical research to accurately assess the effectiveness of medical interventions (Conzemius and Evans 2012).

3.7 ­Types of Pain Pain can be classified based on the site of origin. Pain can also be classified based on its duration of action: acute or chronic, adaptive or maladaptive, and physiologic or pathologic. Here we describe the several different types of pain based on both etiology and the more ­arbitrary duration.

3.7.1  Somatic, Visceral, and Referred Pain Nociception stemming from an injury to the skin, muscles, joints, and deep tissues is somatic pain. Somatic pain arising from the skin and muscles is conducted via A-­delta and C fibers and is often discrete and easy to localize. This is due to the high degree of somatotopy or point-­to-­point correlation of a body area with a specific location in the CNS (Woolf 1995; Lemke 2004). When you receive an injury from a scalpel, it is very easy to pinpoint exactly where the injury is located. Skin is a protective covering that has evolved to respond and shield animals from external insults. Nociceptive information is detected and processed, and avoidance strategies are instituted. Most pain research has been done on superficial-­type stimulation, and until recently, this information was erroneously extrapolated to include visceral pain as well. We now know that these two types of pain are very different. Noxious stimulus originating in the internal organs of the thorax or abdomen is visceral pain. Visceral pain is conducted via C fibers. Visceral pain is often dull, aching, or

burning pain that is difficult to localize due to the low degree of somatotopy. Visceral pain is different because the viscera are not exposed to comparable insults but instead are the target area for many disease processes (Lamont et  al.  2000). The protective function of visceral pain is not as obvious as it is for somatic pain; therefore, visceral pain poses a challenge to healthcare professionals in both human and veterinary fields. It is interesting to note that many life-­threatening forms of tissue destruction like intestinal perforation and visceral neoplasia are not painful by themselves, but a non-­life-­threatening event like intestinal distension (gas) is perceived as  painful. Visceral organs are sensitive to ­distension (e.g. intestines, gallbladder, and urinary bladder), ischemia (e.g. heart attack in humans), and inflammation as is seen with nephritis or pancreatitis. Visceral pain may manifest as diffuse pain, general malaise, or nausea, and it may be referred to the somatic structures. Referred pain is often associated with visceral pain whereby the sensation of pain is felt elsewhere besides the area of injury. For example, liver pain or diaphragm pain may be referred to the shoulder and myocardial ischemia to the left arm (Lamont et al. 2000). Visceral organs do not have A-­delta fibers but utilize C fibers to carry nociceptive information. These fibers both converge on the same area of the spinal cord where A-­delta fibers carry somatic information and C fibers carry visceral and somatic information. The brain may then localize the visceral pain to a somatic structure due to the high somatotopy of the somatic neurons (Muir 2009).

3.7.2  Physiological/Adaptive/Acute Pain Physiological, adaptive, and acute pain are all synonymous terms for a pain that typically results from inflammation or injury and has a biologically useful function-­to prevent further damage and to enable healing. Typically, this type of pain is also meant to protect and

3.7 ­yersoo Pain

encourage an individual to move away from harmful external stimuli, which may induce further tissue injury and become life-­ threatening. The term acute refers to duration and onset, such as postsurgical pain. All three terms correlate to an adaptive (protective) response and are often used interchangeably (Monteiro et al. 2022). Even though acute pain serves an initial purpose, it should be managed to avoid development into pathologic or chronic pain syndromes (Muir 2009; Lamont et al. 2000). Characteristics of adaptive pain (Monteiro et al. 2022): ●●

●●

●●

●●

Associated with potential or actual tissue damage. Purpose: to rapidly alter the animal’s behavior to avoid or minimize damage and optimize the conditions in which healing can take place. Varies in severity and is proportional to the degree of tissue damage. Self-­limiting: diminishes with healing and ceases when healing is complete.

3.7.3  Pathological/Maladaptive/ Chronic Pain Pathologic, maladaptive or chronic pain may arise from tissue damage and inflammation where a certain degree of peripheral and central sensitization accompanies injury. This pain can be diffuse, disproportionate to the degree of  injury, and debilitative  – often continuing beyond the resolution of the inflammatory ­process. Traditionally, chronic pain has been defined as pain lasting longer than three months, however this definition is evolving as there is nothing that changes from acute to chronic pain as pain itself changes on a continuum. However, the terms pathological, maladaptive or chronic pain is commonly used to describe pain where sensory pathways have likely been pathologically altered. As mentioned in the beginning of this chapter there is some conversation in classifying certain types of pain, like chronic pain, as a disease itself (Melzack et al. 2001; Patel 2010; Monteiro et al. 2022).

Characteristics of (Monteiro et al. 2022): ●●

●●

●● ●●

maladaptive

pain

Persists beyond the expected course of the acute disease. Not associated with healing and no clear end and can be associated with recurrent or long-­ standing disease conditions. Can exist without a cause. Chronic pain significantly affects a patient’s quality of life and tends to be debilitating and poorly responsive to traditional analgesic therapy.

3.7.4  Neuropathic Pain Neuropathic pain arises from damage to or dysfunction in the nervous system because of trauma, infection, ischemia, cancer, untreated diabetic neuropathies, or chemically induced (chemotherapy). Some types of neuropathic pain may develop when the peripheral nervous  system (PNS) becomes damaged. This can cause the nociceptors to transmit pain signals repeatedly leading to hypersensitivity. Prolonged central sensitization because of ongoing ectopic C fiber stimulation either at the site of injury or in the dorsal horn of the spinal cord can result in neuropathic pain (Woolf  1995). Neuropathic pain can also be a result of significant, prolonged acute pain that leads to peripheral sensitization. This abnormal peripheral input then leads to abnormal central processing and the persistence of hypersensitivity associated with neuropathic pain. Dorsal horn structural reorganization where innocuous A-­beta fibers terminate in the areas of the dorsal horn normally occupied by A-­delta and C fibers may provide an explanation for neuropathic pain (Melzack et al. 2001). Sleep disturbances, anxiety, and depression are frequent and severe in patients with neuropathic pain, and quality of life is more impaired in patients with chronic neuropathic pain than in those with chronic non-­neuropathic pain that does not come from damaged or irritated nerves (Finnerup et al. 2016).

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3.7.5  Radicular Pain Aside from neuropathic pain, radicular pain must also be mentioned. Both neuropathic pain and radicular pain consist of nerve damage, but the difference comes down to the location of the problem. If there is damage at or near the nerve root along the spine, it is considered a radiculopathy. Neuropathy is seen outside of the spinal cord in the peripheral nerves. In veterinary patients, we see this often as nerve root syndrome in dogs. Lateralized disc herniation, foraminal stenosis, and malignant as well as benign nerve sheath tumors are some of the most important triggers described. The clinical signs of a nerve root syndrome are characterized by monoparesis in combination with progressive lameness, which may be accompanied by an elevation of the affected limb (Eberhardt et al. 2019).

3.7.6  Chronic/Persistent Postsurgical Pain While acute pain following surgery usually subsides within 1–2 weeks with effective treatment, in some cases, this acute postsurgical pain may not follow the typical course of tissue healing and instead evolve into a chronic or persistent state. This chronic or persistent postsurgical pain (CPSP) (PPSP) is characterized as pain that remains localized to the surgical area, a nerve’s innervation within that area, or a dermatome following deeper somatic or visceral surgery, lasting for at least 3–6 months. Establishing a universally accepted definition of CPSP is crucial for guiding research in this area. The initial definition, proposed by Macrae and Davies in 1999, includes criteria such as the development of pain following surgery, duration of pain for at least 2  months, exclusion of other pain causes, and confirmation that the pain is not from a preexisting ­condition. However, this original definition assumed that CPSP is merely the continuation of acute postsurgical pain. Yet, research ­indicates that some human patients initially experience mild or no pain post-­surgery, with

different or new pain sensations emerging weeks or months later. This disconnect between early and later pain outcomes underscores the need to explore biopsychosocial risk factors associated with CPSP. In human medicine, chronic postsurgical pain (CPSP) has emerged as a highly researched area, especially in the context of primary pain prevention. Its prevention is now a key research focus in anesthesia and perioperative medicine. However, in veterinary medicine, there has been a slower recognition of CPSP’s potential relevance, particularly among veterinary surgeons and specialists in veterinary anesthesia. The last two decades have seen a significant rise in the complexity and invasiveness of veterinary surgeries. Procedures such as thoracotomies, mastectomies, amputations, and reconstructive surgeries, which are linked to a high incidence of CPSP in humans, are now common in veterinary practice. Studies frequently utilize rats as models for chronic neuropathic pain research and routine surgical practices are performed on young animals in agricultural settings. These procedures often involve damage to sensitive tissues and are sometimes conducted with insufficient pain management, raising concerns about the broader implications for animal welfare. This should make us question, are we overlooking a significant issue in clinical, ethical, and welfare terms in animals? CPSP was identified in humans because the right questions were asked. It’s worth considering whether this lack of inquiry into CPSP in veterinary ­practice is due to a lack of reflective clinical practice or if CPSP is a problem exclusive to humans. CPSP is undeniably complex, with multiple risk factors identified across preoperative, intraoperative, and postoperative ­periods, encompassing genetic, demographic, psychosocial, acute pain, clinical, and surgical factors. There’s a prevailing belief that the intricacy of these risk factors and the involvement of genetic, demographic, and psychosocial elements imply a lower risk of CPSP in

3.8 ­The Microbiome and Pain Pathophysiolog

animals. This presumption assumes that animals do not share similar psychosocial or genetic vulnerabilities. However, as we continue to research and discover more similarities between animal psychosocial and genetic vulnerabilities seen between humans and animals this question should no longer be ignored (Molsa et al. 2013; Clark 2021).

3.7.7  Complex Regional Pain Syndrome Complex regional pain syndrome (CRPS), previously known as reflex sympathetic dystrophy, sympathetically maintained pain, causalgia, and Sudeck’s atrophy, is a severe neuropathic pain syndrome. The diagnosis of CRPS in humans largely relies on clinical assessments that align with criteria set by the IASP. These criteria include experiencing chronic pain that is significantly more intense than the initial injury, heightened sensitivity to painful stimuli (hyperalgesia), pain arising from normally nonpainful stimuli (allodynia), and evidence of autonomic dysfunction. This dysfunction can manifest as changes in skin temperature, sweating abnormalities, edema, and vasospasm, along with changes in skin appearance. CRPS typically develops following an acute injury but can also arise without any clear initiating event. While there have been reports of CRPS in dogs, horses, and cows and has been recognized by human healthcare professionals for more than a hundred years, the exact mechanisms underlying its development are not fully understood. Consequently, the treatments currently available for CRPS have yet to meet the desired levels of efficacy (Bergadano et al. 2006; Liu et al. 2021; Collins et al. 2006).

3.7.8  Social Resilience and Pain Social resilience in the context of pain refers to an individual’s ability to maintain or regain social and psychological well-­being while experiencing chronic pain. This concept encompasses several dimensions. One of the

key aspects of social resilience is the presence of a strong support system. This can include human or animal family or friends. This type of support provides emotional, informational, and sometimes physical support, helping individuals cope with the daily challenges posed by chronic or acute pain. When an animal can engage in social activities it can foster a sense of belonging and purpose that can be vital for social animals dealing with a pain state. In the context of human social resilience, which involves the ability to communicate effectively about one’s pain experience, set boundaries, and advocate for oneself in social and medical settings, this can be more challenging but not impossible when it comes to nonverbal animals. This would include maintaining and building relationships with the animal despite the limitations that pain might impose and using multiple standardized pain scoring tools to help assess the level of pain an animal is experiencing to intervene effectively. This may also include more astute attention to the animal’s preferences in bedding, food, and even interactions with other animals or humans. Essentially, when an animal feels supported, they are likely to have better outcomes. Veterinary nursing staff are in a unique position, often already providing some level of social resilience with the nursing care provided. This can be enhanced by incorporating more affection to animals in our care, taking and communicating more detailed nursing notes for the next staff member or owner to follow and providing familiar things like a blanket or toy from home (Sturgeon and Zautra 2016).

3.8 ­The Microbiome and Pain Pathophysiology The evolution of technology has allowed researchers to understand more about the microbes living in the large intestine, known as the gut microbiome. While this microscopic

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community may not seem relevant to pain physiology, the functions completed by these microorganisms can influence multiple physiological systems, including pain.

3.8.1  What Is a Microbiome? A microbiome is a microscopic community of bacteria, fungi, protozoa, archaea, and viruses that create a complex ecosystem. These microscopic communities can be found residing in all environments including soil, plants, and animals. They thrive in controlled aerobic, and anaerobic environments with some types of microbes being facultative, allowing them to  alter their ability to survive and function in  either type of environment (Ziese and Suchodolski  2021). These microscopic communities have been identified in several mammalian body systems including the respiratory tract, reproductive organs, oral cavity, urinary tract, skin, and gastrointestinal tract with over 100 trillion microbes residing in this system alone. This list is not exhaustive as new innovations allow us to discover microbiomes in organs, and ­systems once thought to be sterile (Ziese and Suchodolski  2021). Gut microbes assist in the physiological and metabolic processes of the host through many interactions. The initial development of the gut microbiome may have an influence on how the host identifies and manages pain with the gut microbiota playing a pivotal role in the regulation of maturation, morphology, and immunological function of the immune system and the microglia (DeGruttola et al. 2016). Pioneer microbes that first inhabit the gut are crucial in developing and training the immune system. Consider the different microbial exposure between vaginal and surgical birth. Pets born via vaginal delivery are exposed to species-­ specific vaginal, oral, and skin microbes while those being born via caesarean section are exposed to more environmental and human-­ specific microbes. The gut contains the largest number of immune cells and is well vascularized with both blood and lymph vessels, giving

the pioneer microbes large influence over how the immune system will react in the future (Suchodolski 2011). What is becoming a larger topic of discussion is if appropriate intestinal microbes are disrupted during the growth life stage, the normal development and function of the intestinal immune system is impaired. There are increasing findings of these perturbations leading to an increased risk of a disease state later in life (Stavroulaki et al. 2021). Several factors influence the state of a microbiome including genetics, birthing presentation (vaginal or surgical), age, sex, environment, stress, antibiotic therapy, and nutrition (Ziese and Suchodolski  2021; Tengeler et  al.  2018). Nutrition is an important factor as microbes can ferment lumen contents, including contents that are not digestible by mammalian enzymes, such as fiber. Much like upper tract digestion, microbes can produce digestive enzymes and perform chemical reactions on lumen contents. By adjusting the type of nutrients in the lumen, we can alter the density of microbes and therefore, fluctuate the level of beneficial or potentially harmful functions completed. See Chapter  17 for further details about nutrition to support pets. One main interaction tool is the microbial production of metabolites. Metabolites are the  chemicals or products of fermentation. Fermentation is the ability of microbes to digest or chemically break down nutrients that reach the colon. These metabolites have multiple functions including the provision of energy or  the ability to be utilized in a variety of ­physiological functions for the host, including functioning as signaling molecules (neurotransmitters and neuromodulators) and regulating peripheral and central sensitization (Guo et al. 2019). The microbes can also use metabolites to communicate with each other. Another recognized influence of the microbiomes on the host is the cumulative genetic material of all the microbes in one animal’s singular microbiome, with approximately 200 times the genetic material in the microbiomes compared to a human genome. For example, in mice, it is known that

3.8 ­The Microbiome and Pain Pathophysiolog

a depletion of histone deacetylase 3 results in the dysregulation of intestinal epithelial cell gene regulation. This regulation is dependent on the gut microbiota. A line of mice was bred to specifically be low in histone deacetylase 3. One group in this line had normal gut microbiome development while the other was germ-­ free. “Germ-­free” animals are “sterile” and do not have a gut microbiome. Interestingly, the group with the gut microbiome showed dysregulated host gene expression and disrupted homeostasis while the “germ-­free” mice did not (Nichols and Davenport 2021).

3.8.2  Determining “Healthy” in a Microbiome The health status of pets is correlated with the state of the gut microbiome, as is the ability of this “super organ” to influence remote organs and physiological, metabolic, and immune responses (Ziese and Suchodolski  2021). A healthy microbiome in a patient is identified by  a highly diverse (many types of microbes) and rich or dense (adequate, even growth) gut microbiome. Currently, bacteria that are shed in the feces (fecal microbiome) are being utilized clinically and in research as a mirror of what is happening in the gut. Fecal material is a good resource, with 1 g stool containing 100 billion microbes, and is easily accessible (Allaband et al. 2019). The creation of a healthy reference set requires a subset of the population of that same animal species to have their fecal genome sequenced with strict control measures to ensure the accuracy of the results. A fecal microbial reference range identifies the core bacteria (most frequently identified) and the general volume of core bacteria that are observed routinely in a very large healthy group or species; many test subjects is required to show a true average range for that species population. “Core” bacteria have been identified in humans, dogs, and cats. These core bacteria, when found in normal ranges are reported in pets experiencing good health and normal physiological and metabolic processes. Interestingly, there is not a

direct correlation between an asymptomatic pet and a normal fecal microbial. Pets may not be showing outward symptoms but can have a significant imbalance in their gut microbiome. Further research is required to determine whether disease leads to dysbiosis or if fecal microbial imbalances in asymptomatic pets are a pre-­indicator of disease (Ziese and Suchodolski 2021).

3.8.3  Gut Microbiome Imbalance or Dysbiosis Imbalances in the gut microbiome are complex, with imbalances even being found in pets that are considered healthy. When there is an imbalance in the microbiome that is associated with a disease state, gut dysbiosis can be diagnosed. Multiple factors influence the balance of the gut microbiome including genetics, birthing ­presentation, age, sex, environment, stress, antibiotic therapy, and nutrition (Ziese and Suchodolski 2021; Tengeler et al. 2018). These influencers are identified as crucial perturbations in human research associated with gut dysbiosis in depression, autism spectrum disorder, oral health, chronic obstructive pulmonary disease (COPD) asthma, pneumonia, dermatological, Parkinson’s, obesity, cardiovascular, diabetes, rheumatoid arthritis, Alzheimer’s, multiple sclerosis, hepatic associated disorders (bile acid dysmetabolism), cancer, inflammatory bowel disease (IBD), colitis, Crohn’s, and bacterial infection due to bacterial translocation (Ziese and Suchodolski 2021; Ma et al. 2019). A state of dysbiosis is an alteration from ­normal for that species and specific host that is associated with a disease state. Several findings indicate that gut microbiota perturbations may produce a local, and subsequently, systemic inflammation (Sánchez Romero et  al.  2021). There are generally three types of dysbiosis observed. These states can occur singularly or concurrently: 1) Expansion of pathobionts. Pathobionts may  create harmful effects when given

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the  opportunity to expand. For example, facultative species of Escherichia sp. can flourish post-­antibiotic therapy (Petersen and Round 2014); 2) Loss of beneficial microbial organisms. Core bacteria have specific roles in supporting host health including digestion of nutrients, completing microbial transformations, and influencing inflammation. For example, a loss of core anaerobes that ferments dietary fibers may result in a decreased production of short-­chain fatty acids (SCFA) allowing for dysregulation of the Treg pool and inducing an inflammatory state (Petersen and Round 2014); 3) Loss of diversity. With multiple varieties of microbiota eliciting health benefits to the host. Having a more diverse and complex pool of organisms has been shown to provide maximum benefits (Petersen and Round 2014; DeGruttola et al. 2016). As previously mentioned, there are multiple factors that can influence the development of dysbiosis. It is the result of these perturbations that induce or perpetuate a disease state by the increase in proinflammatory microbes, a reduction of commensal microbes that promote immune tolerance mechanisms and protect from an inflammatory response in the host (DeGruttola et al. 2016). Antimicrobial therapy is a main gut influencer that creates significant, long-­term dysbiosis and may affect the pain status of a pet. A study in mice (Verdú et al. 2006) found antibiotic administration early in life produced long-­lasting enhancement of visceral pain (Verdú et al. 2006; Guo et al. 2019).

cells, the intestines, and the intestinal microbiota, and the ability to communicate reciprocally; gut functions can alter the function of the brain and neurological system, and the brain is able to influence the functions of the  gut and microbial composition. The gut microbiome is identified as being involved in visceral pain, chronic pain, neuropathic pain, and opioid tolerance (DeGruttola et al. 2016). The gut microbiota can modulate peripheral sensitization through (i) gut microbiota-­ derived mediators that regulate neuroinflammation in the peripheral and central nervous system, and (ii) direct modulation of the ­dorsal root ganglia neuronal excitability (DeGruttola et al. 2016). In the brain, endothelial cells, pericytes, microglia, astrocytes, and infiltrating immune cells can be activated by gut microbiota-­derived mediators, which contribute to the development of neuroinflammation (DeGruttola et al. 2016).

3.8.5  Microbial Derived Mediators Gut microbiota-­derived mediators play a large role in how this axis works including their ability to, directly and indirectly, regulate peripheral sensitization of pain (Guo et  al.  2019). Gut microbiota-­derived mediators include microbial by-­products (ex. pathogen-­associated molecular patterns [PAMPs]), microbial-­derived metabolites (ex. SCFA), secondary bile acids, and neurotransmitters or neuromodulators (ex. GABA, serotonin [HT-­5]). Depending on the type of mediator activated, pain may be enhanced or inhibited (Agus et al. 2021; Guo et al. 2019).

3.8.4  The Gut-­Brain Axis

3.8.6  Pathogen-­Associated Molecular Patterns (PAMPs)

In both physiological and pathological conditions, the gut microbiota is becoming one of the most important players in host health with the recognition of bidirectional interactions between the gut microbiome and the brain (Ma et  al.  2019). This axis utilizes multiple organs including the brain, glands, immune

PAMPs are gut microbiota-­derived mediators  obtained from parts of bacteria cell walls  including (i) lipopolysaccharides, (ii) lipoteichoic acid, (iii) peptidoglycan, and (iv) β-­glucan. PAMPs release locally and navigate through the circulatory system to bind with toll-­like receptors (TLRs) found on immune

3.8 ­The Microbiome and Pain Pathophysiolog

cells in the dorsal root ganglia, activating the release of pro-­inflammatory cytokines and chemokines. This indirectly activates or sensitizes sensory neurons in the dorsal root ganglia contributing to peripheral sensitization in chronic pain conditions (Guo et al. 2019).

3.8.7  Microbial-­Derived Metabolites A microbial-­derived metabolite is a chemical compound that results from the metabolism of a nutrient, drug, chemical, or tissue. Generally speaking, a gut microbial metabolite is created from the metabolism (fermentation process) of nutrients in the colon by the microbiota. The type of metabolite produced is dependent on the type of bacteria metabolizing the nutrient and the type of food source metabolized. The total volume or collection of metabolite production (metabolome) will influence the overall effect it has on the host. There are a few metabolites of interest when investigating the role of gut microbiota in pain such as SCFA, secondary bile acids, GABA, and serotonin (5-­HT) (Figure 3.6). SCFAs are becoming well known for the benefits they exhibit on the host, including the ability to attenuate inflammation and regulate pain sensation (Guo et al. 2019). SCFAs are mainly derived from the fermentation of complex carbohydrates (polysaccharides or nondigestible fiber sources) by anaerobic bacteria (Guo et al. 2019). The three most common forms of SCFAs are butyric acid (butyrate), acetic acid (acetate), and propionic acid (propionate). As important mediators of pain regulation, SCFA acts on free fatty acid receptors 2 and 3 to modulate neurological signaling (Mishra et al. 2020). They can regulate leukocyte functions, including the production of a variety of cytokines (TNF-­𝛂, IL-­2, IL-­6, and IL-­10), eicosanoids, and chemokines (Guo et  al.  2019). Of particular interest, SCFAs are one metabolite that can cross the blood–brain barrier; they are involved in multiple immune and metabolic pathways. Future treatments with SCFA may  aid in the regulation of neuro-­immuno endocrine function (Silva et al. 2020).

The bile acid recycling system is highly effective, with 90–95% of conjugated primary bile acids (BA) absorbed in the small intestine, and then 95% of the absorbed BA recycled by the liver for re-­conjugation with an amino acid. The remaining 5–10% of conjugated BAs that are not absorbed in the small intestine reach the gut microbiota in the large intestine. Specific bacteria function in multiple microbial transformations on conjugated primary bile acids to create secondary bile acids, which are then absorbed in the large intestine by passive transfer. This system is particularly important for gut microbial balance and proper digestion of nutrients. It is becoming recognized that bile acid metabolites may regulate pain through the G protein-­coupled receptor 1 (TGR5). For example, secondary bile acid, deoxycholic acid (DCA), in peripheral macrophages leads to the release of endogenous opioids resulting in analgesia for the host (Guo et al. 2019).

3.8.8  Neurotransmitters or Neuromodulators Some metabolites produced by gut microbiota can function as neurotransmitters or neuromodulators, altering neurological functions. Not all neurotransmitters produced by gut microbiota are able to cross the blood–brain barrier through neurotransmitter precursors followed by a conversion into an active neurotransmitter like SCFA. Instead, they can work locally in the gut acting on specific receptors that transfer information from the periphery to the spinal cord or brain (Ding et  al.  2020). Microbiotas can influence the activity of the enteric nervous system through the production of locally acting neurotransmitters such as GABA, 5-­HT, melatonin, histamine, and acetylcholine. Additionally, gut microbiota can generate a biologically active form of catecholamines in the lumen of the gut (Carabotti et al. 2015). GABA is a non-­protein amino acid (an amino acid that is not coded with DNA) and can be found in plants, animals, and

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3 Pain Physiology and Psychology Blood Brain Barrier Endothelial cell

Pericyte

Glu

Neuron

GABA

Astrocyte Brainstem

Vagus nerve Spinal cord

Circulation

Cytokines

IPAN

Immune cells

Enteric muscles 5-HT

Gl peptides

Gut epithelium EEC

EC

Enterocyte Dietary GABA

GABA Dietary proteins and Glu

Glu

Gut microbiota

Gut lumen

Figure 3.6  Potential pathways for luminal Glu/GABA in the gut (of either dietary or gut–microbiota origin) to influence the nervous system (see text). 5-­HT, serotonin; EC enterochromaffin cell; EEC, enteroendocrine cell; GI, gastrointestinal; IPAN; intrinsic primary afferent neuron. Source: Adapted from https://www.nature. com/articles/nrn3346 / last accessed Feb 21, 2024.

microorganisms. One of GABA’s well-­known physiological and psychological functions is being a chief inhibitory neurotransmitter in the central nervous system that can be produced through microbial transformation (decarboxylation) by specific bacteria (Lactobacillus spp., Bifidobacterium dentium, and Bifidobacterium

spp.) (Guo et al. 2019) GABA plays a role in the perception of pain and anxiety; dysfunctions in normal GABA metabolism are involved in increased anxiety and depressive conditions in humans (Duranti et al. 2020). 5-­HT is an important neurotransmitter that can be produced by Candida spp., Streptococcus spp., Escherichia

3.8 ­The Microbiome and Pain Pathophysiolog

spp., and Enterococcus spp. In peripheral ­tissues, 5-­HT acts as a pain-­inducing mediator with subtypes having the ability to affect different neurological areas. While it is generally accepted that increased tryptophan in the diet is directly correlated with increased serotonin levels in the brain, it is the gut microbiota that can affect the metabolism of tryptophan as a precursor of serotonin. In this manner, the gut microbiota is able to manipulate serotonergic signaling in the CNS (Ding et al. 2020).

3.8.9  Endocannabinoid Axis The ECS is involved in multiple functions including pain-­relieving and anti-­inflammatory functions Microbial metabolites produced in the gut consisting of more than 100 lipid mediators and 50 protein metabolites play a large role in the proper function of the ECS. The collection of these metabolites, 100 endocannabinoid-­like mediators, 12 receptors, and more than 20 anabolic and catabolic metabolic enzymes make up the endocannabinoidome (Della Rocca and Di  Salvo  2020; Guida et  al.  2020; Iannotti and Di Marzo 2021; Schiano Moriello et al. 2022). Both the endocannabinoid and the gut ­microbiome function to control intestinal homeostasis and influence energy metabolism and neuroinflammatory responses during ­physiological conditions (Schiano Moriello et al. 2022). Changes in the gut microbiome are associated with corresponding alterations in endocannabinoid and endocannabinoidome signaling, which in turn perpetuates a dysbiotic state (Iannotti and Di Marzo  2021). This has  been observed in studies with mice where  endocannabinoidome signaling was altered post a fecal microbial transplant (FMT)  enema  resulting in changes in the mRNA expression of some endocannabinoidome receptors including an increase in CB1, while two G protein-­coupled receptors were decreased (Iannotti and Di Marzo  2021). Akkermansia muciniphila is a bacterium that has been positively correlated with an improved metabolic profile, and the presence

of endocannabinoids and endocannabinoid-­ like mediators in the gut (Guida et al. 2020). One function of this axis is the prevention of negative metabolic effects, including managing systemic inflammation induced by dysbiosis (Iannotti and Di Marzo  2021). With the connection between obesity, inflammation, and pain, this connection is important to acknowledge. In patients with osteoarthritis, a local and systemic inflammatory state is elicited by dysbiosis in the gut microbiome that is exacerbated by barrier dysfunction and the contact of microbes and metabolites to the intestinal epithelium. This inflammatory state is associated with the presence of lipopolysaccharides, and lipopolysaccharide-­binding protein in the serum and the synovial fluid in affected patients. The proinflammatory microbiome profile appears to play a role in the severity of pain and maintains inflammatory disease both locally in the joints and systemically (Sánchez Romero et  al.  2021). The ECS involvement in inflammatory disease is also observed in the homeostasis of the feline oral mucosa in healthy cats. Feline chronic gingivostomatitis is a disease that results in severe mucosal inflammation and pain and is ­associated with oral dysbiosis and up-­regulated cannabinoid and cannabinoid-­related receptors (Polidoro et al. 2021). Interestingly, another endocannabinoidome function involves alterations in GI microbial diversity that can possibly contribute to a pet’s anhedonia (the ability to feel pleasure) and amotivation (the lack of motivation) behaviors (Silva et al. 2020; Ding et al. 2020). An alteration, usually a decrease, in normal microbial diversity has been associated with a variety of  mood disorders in humans (Carabotti et al. 2015). A study in mice using unpredictable chronic mild stress showed phenotypic alteration in their fecal microbiome. When the fecal material was transferred to naive ­recipient mice via FMT enema cellular and behavioral changes along with a decrease in endocannabinoid signaling were observed in the recipient mice. These changes were then reversed, and

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the behaviors were alleviated by the addition of a strain of the Lactobacilli genus (Carabotti et al. 2015).

3.8.10  Pain Medication and the Microbiome Pain medication can also cause disruptions to the normal functions of gut microbes. It has been well-­accepted that GI-­related symptoms or opioid-­induced intestinal dysfunction may occur. Recent research is finding that ­long-­term use of opioids is associated with microbial dysbiosis in humans and mice.

Morphine-­mediated TLR in epithelial cells impairs the intestinal epithelial barrier and allows an increase in bacterial translocation. Additionally, there is an increase in TLR that  mediates gut inflammation. This results in the release of additional pro-­inflammatory cytokines, and an alteration of the regulation of neuronal excitability in the peripheral ­nervous system. Studies in humans suggest that the use of opioids as analgesia in patients  with severe barrier dysfunction may experience worsening GI symptoms, and an increased risk of both infections and mortality (Guo et al. 2019).

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Muir, W.W. (2009). Physiology and pathophysiology of pain. In: Handbook of Veterinary Pain Management, 2e (ed. J.S. Gaynor and W.W. Muir), 13–41. St. Louis, MO: Elsevier. Nederkoorn, C., Vancleef, L., Wilkenhöner, A. et al. (2016). Self-­inflicted pain out of boredom. Psychiatry Research 237: 127–132. https://doi.org/10.1016/j.psychres.2016.01.063. Nichols, R.G. and Davenport, E.R. (2021). The relationship between the gut microbiome and host gene expression: a review. Human Genetics 140: 747–760. https://doi.org/10.1007/s00439­020-­02237-­0. Patel, N. (2010). Physiology of pain. In: Guide to Pain Management in Low-­Resource Settings (ed. A. Kopf and N.B. Patel), 31–35. Washington, DC: International Association for the Study of Pain. Petersen, C. and Round, J.L. (2014). Defining dysbiosis and its influence on host immunity and disease. Cellular Microbiology 16 (7): 1024–1033. https://doi.org/10.1111/cmi. 12308. Polidoro, G., Galiazzo, G., Giancola, F. et al. (2021). Expression of cannabinoid and cannabinoid-­related receptors in the oral mucosa of healthy cats and cats with chronic gingivostomatitis. Journal of Feline Medical Surgery 23 (8): 679–691. https://doi.org/10. 1177/1098612X20970510. Raffaeli, W. and Arnaudo, E. (2017). Pain as a disease: an overview. Journal of Pain Research 10: 2003–2008. https://doi.org/10.2147/jpr. s138864. Rasmussen, A.H., Petersen, L.K., Sperling, M.K. et al. (2023). The potential effect of walking on quantitative sensory testing, pain catastrophizing, and perceived stress: an exploratory study. Scandinavian Journal of Pain 23 (4): 751–758. https://doi.org/10.1515/ sjpain-­2023-­0039. Sánchez Romero, E.A., Meléndez Oliva, E., Alonso Pérez, J.L. et al. (2021). Relationship between the gut microbiome and osteoarthritis pain: review of the literature. Nutrients 13 (3): 716. https://doi.org/10.3390/nu13030716.

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4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species Stephen Niño Cital1,2,6, Ian Kanda3, Taly Reyes4, Jessica Birdwell4, and Mary Ellen Goldberg5 1

Howard Hughes Medical Institute at Stanford University, Stanford, CA, USA Veterinary Anesthesia Nerds, LLC, Sheridan, WY, USA 3 Pet Hospital of Penasquitos, San Diego, CA, USA 4 The College of Veterinary Medicine University of Tennessee, Knoxville, TN, USA 5 Mannheimer Foundation Inc., Boynton Beach, FL, USA 6 Remedy Veterinary Specialists, San Francisco, CA, USA 2

4.1 ­Introduction The official definition of pain by the International Association for the Study of Pain (IASP) is: “An unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage.” The definition also acknowledges that the “inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain.” In verbal humans, the backbone of pain assessment is self-­reporting. Assessing pain in animal patients or nonverbal humans is therefore inherently complicated by their inability to self-­report. No matter the species, the pain experience affects patients multidimensionally via physiological and affective components. The various aspects, or domains, of an individual’s pain experience may include cognitive, affective, behavioral, functional, physiological, sensory, and socio-­cultural (human–animal bond or interactions) dimensions, which can then be measured and interpreted to help guide treatment. Historically, the evolution of assessing pain, or even the

understanding that animals indeed feel pain, has come a long way in veterinary medicine. No longer should we view pain as merely a superficial perception of an unpleasant sensation but rather a nuanced, highly integrated experience impacting patients physically, cognitively, and socially. Further research is still necessary to fully elucidate ideal pain assessments based on various domains  – particularly for the numerous species, and breed-­specific personality animals may have that contribute to their pain experience. As of now, using multiple tools to assess pain is recommended. It is also worth noting in the clinical realm of analgesic trials, by offering a particular analgesic to a potentially painful animal that does not appear to have changed the status of the animal, does not mean a different analysis with a different mechanism of action is not warranted. In this chapter, we discuss the current tools available to assess the pain experience in animals. We want to encourage the adoption of more than one tool to more adequately and appropriately identify pain and address it on an individualized basis for our patient populations.

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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4.2 ­Pain Domains A thorough pain assessment utilizes multiple domains of pain for the evaluation. There are three broad domain categories: pain intensity and affect, temporal features, and bodily location(s) (Fillingim 2017). Within these three broad domains are other domain types used in creating pain-­scoring tools or as independent features to assess a patient in conjunction with better-­defined or validated clinical assessment tools. No “gold standard” for a specific domain’s utilization is yet accepted in animal pain assessments. The domains impacted by pain vary significantly with each pain condition and the context in which they are being assessed.

4.2.1  Pain Intensity and Affect This domain attempts to measure the intensity of the pain using categorical scales such as mild, moderate, and severe, or using numerical ­ratings such as ranking pain from 1 to 10, with the highest number being the most excruciating pain level. The affect portion describes how unpleasant or disturbing the pain is to a patient. For this measurement, we often see visual analog scales (VASs) used where facial expression or body ­posture are used to assess a “level” of pain.

4.2.2  Temporal Dimensions Temporal dimensions are related to the time or frequency of pain. This dimension evaluates time from the onset of pain – or when pain care is sought – and if the pain is episodic, persistent/ chronic, or constant with fluctuations in intensity. This dimension is less commonly assessed in veterinary patients due to the complexity of measuring nonverbal species.

4.2.3  Location and Bodily Distribution of Pain These domains focus on the areas or regions of pain and, more broadly, how widespread it is from its etiology, if there is one. This domain

can be measured in able humans by having patients color or draw on a human figure outline where the pain is and how intense it is. In animal patients, this can be subjectively assessed by performing a detailed physical exam, noting areas of sensitivity and the patient’s reactions to touch or manipulation. Thermal imaging may also help elucidate painful areas. Under these three broad domains are other domains/dimensions that help fine-­tune the creation of assessment tools. Examples in animals include: –– Overall activity –– Movement and mobility (limb use or quality of use) –– Ability to perform the activities of daily living –– Cognitive function –– Affective states (fear, anxiety) –– Interactions with other animals and humans –– Physiological function –– Sensory processing –– Sleep Pain in all its forms must be appraised individually with the understanding that we, as human caregivers, cannot fully appreciate how a particular species perceives the experience. A conscious experience of past, present, or future pain (pain catastrophizing) is subject to various emotions that can cause distress or mental turmoil even without noxious stimuli. We now understand that fear, anxiety, memory, and stress can modify the pain experience (Monteiro et al. 2022; Lascelles et al. 2019).

4.3 ­Disposition and Personality Pain assessments or outcomes based on an animal’s disposition or personality are a growing study area. How the animal interacts with the world around it or with its caregivers may expound a patient’s response to a painful experience. Tissue injury can lead to pain, prompting animals to display protective behaviors like lameness. However, since an animal’s subjective

4.3 ­ispositionand Personalitt

experiences of pain can’t be directly measured, research in this field and veterinary evaluations often depend on behavioral, clinical presentation, or vital signs to gauge pain levels. This approach presumes that the extent of pain is directly related to the degree of injury. However, this perspective overlooks the potential influence of individual personality traits and coping mechanisms (Finkemeier et al. 2018). Ensuring proper animal welfare, particularly in veterinary practices, involves the vigilant monitoring and management of pain. This process depends on observing various behavioral and physiological signs, among other domains. Notably, distinct physiological traits can influence consistent behavioral variations and patterns, often termed as “personality.” Such personality traits could potentially influence the accuracy of pain assessments. A study on dog personalities involved 20 dogs observed post-­castration in a veterinary clinic. Their core body temperature was monitored through infrared thermography initially upon arrival, then 15 minutes post-­extubation, and subsequently every 30 minutes until they were collected by their owners. Concurrently, their recovery behavior was evaluated using the Short-­Form Glasgow Composite Measure Pain Scale at the same intervals as the thermography checks. The dog’s personalities were assessed using the Monash Canine Personality Questionnaire-­ Revised. Additionally, the dogs’ owners evaluated their pets’ pain tolerance on a five-­point Likert scale. The findings revealed no significant correlation between the pain scores and variations in eye temperature or core body temperature changes, suggesting these measures may not be reliable indicators of a dog’s emotional response to pain. However, dogs with higher extraversion scores exhibited notably higher pain scores, regardless of the similarity in tissue damage experienced, pointing toward a possible personality influence on pain perception. These more extroverted dogs also displayed a significant increase in the temperature of their right eye, hinting at potential brain hemisphere dominance in processing pain. In

contrast, neuroticism did not show any significant relationship with the dogs’ physiological or behavioral responses to pain. The study also found that owner’s predictions about their dog’s pain responses were generally inaccurate. These findings suggest that considering a dog’s personality could be an important factor in effectively assessing their response to pain. However, relying on owner’s assessments of their dog’s pain responses might not be a dependable approach (Lush and Ijichi 2018; Proctor 2012). Assessing feline personalities for their management and care has been relatively underexplored. A study aimed to examine the personalities of pet cats was performed to better understand how this knowledge could apply to their care in domestic settings. Owners of 2802 pet cats from South Australia and New Zealand participated in the study by completing a survey that assessed 52 different personality traits of their cats. Through principal axis factor analysis, five distinct and reliable personality factors emerged: neuroticism, extraversion, dominance, impulsiveness, and agreeableness. The study discusses the potential practical applications of these “Feline Five” personality dimensions in the context of improving the management and welfare of pet cats. For instance, cats scoring high in impulsiveness may be responding to environmental stressors, while those with low scores in agreeableness, which may manifest as irritability, could be indicators of pain or illness. The findings underscored the importance of comprehensive and integrative approaches to understanding feline personality, one that considers both the individual pet and its environment (Litchfield et al. 2017). A horse study first aimed to determine if lameness is a reliable indicator of tissue damage severity or if there is variability in the stoic nature of different individual horses. An experienced veterinarian evaluated horses for lameness, followed by an assessment of tissue damage severity using either x-­ray or ultrasound as part of the clinical diagnostics. Surprisingly, the study found no significant

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correlation between lameness and tissue damage severity. Therefore, stoicism was then defined as the difference between the severity of the injury and lameness scores. The personality of the horses was measured using a questionnaire filled out by their owners, who also rated their horses’ pain tolerance on a 1–5 Likert scale. The results indicated a negative association between neuroticism and stoicism, while extroversion was positively correlated with higher levels of lameness  – suggesting that pain might be more observable in highly extroverted animals. The study, notable as the first to investigate the connection between pain behavior and personality in animals, discusses the need for further research to refine these findings and their significant implications for accurately assessing injury and pain in animals (Ijichi et al. 2014). Another study, this one assessing personality types in goats and their ability to learn various tasks, also showed definitive differences in personality types and their ability to learn. While not an aim of the study, this finding seems to correlate the overall effect an animal’s personality may have on their individual pain experience (Nawroth et al. 2017).

4.4 ­Breed or Species Bias New research has found differences across pain sensitivity thresholds where the researchers identified that breed differences exist in aspects of emotional reactivity. Previous studies have detected breed differences in canine personality traits (e.g. curiosity/fearfulness, sociability, aggressiveness, playfulness) using an array of emotional reactivity tests (Svartberg and Forkman 2002; Svartberg 2006). However, Caddiell et al. (2023b) presented unique findings because of their use of dependent measures of emotional reactivity to assess specific components of fear and anxiety that dogs may experience from non-­painful aspects of being in a veterinary environment, finding that breeds did differ in their behavioral responses

to both the novel object task and the disgruntled stranger test. In the two-­part study looking at how veterinary education and experience shape beliefs (bias) about dog breeds, the researchers found that a significant majority of veterinarians, over 95%, believe that different dog breeds vary in their sensitivity to pain. This belief differs from the perceptions of the public, indicating that such views might be shaped during veterinary education or through clinical practice. Another goal of the study was to analyze how veterinary students’ perceptions of dog breed pain sensitivity evolve during their training, and how these perceptions compare to those of the public and undergraduate students in animal-­health fields. The results showed that veterinary students’ ratings of pain sensitivity across various dog breeds were more in line with those of the veterinary faculty and staff, as opposed to the public and undergraduate students. Additionally, undergraduate students with clinical experience showed a tendency to rate the pain sensitivity of certain dog breeds similarly to veterinary students and professionals. These findings indicate that veterinary education and clinical experience significantly shape perceptions regarding pain sensitivity in different dog breeds. Future research is needed to explore how these beliefs about pain sensitivity are conveyed within veterinary training and whether these beliefs impact the recognition and management of pain by veterinary professionals (Caddiell et al. 2023a). Caddiell also indicated that various dog breeds do exhibit distinct pain sensitivity thresholds as assessed by different Quantitative Sensory Testing (QST) methods. However, these observed differences did not completely correlate with the breed-­specific pain sensitivity perceptions commonly held by veterinarians or the public. Recognizing that pain sensitivity varies among dog breeds is crucial, underscoring the necessity to explore the underlying biological factors contributing to these variations. This knowledge could

4.5 ­tspporia,EmergenceAgitation,and Emergence­elirium

enhance the effectiveness of analgesic treatments tailored to individual breeds. Clinically, this could lead to more precise pain management strategies for dogs. Yet, the existence of misconceptions about canine pain sensitivity raises concerns, as these could negatively influence the recognition and treatment of pain in dogs based on their breed. Future studies are needed and should aim to understand the origins of these breed-­specific pain sensitivity beliefs among veterinarians and further investigate the characteristics of dog breeds that shape these perceptions (Caddiell et al. 2023b). A clinical example of breed pain bias involved a greyhound that had recently undergone an amputation in a veterinary teaching hospital. The animal was in the recovery room and began whining and displaying signs of discomfort. The veterinary students were instructed to give another dose of hydromorphone IV. The dog continued to display signs of pain. The students were instructed to give a micro dose of dexmedetomidine. The dog continued to whine and display signs of discomfort. When faculty was asked what could be going on, the response was “It’s a greyhound, they’re just like that and probably a little dysphoric.” After several minutes with the dog continuing to whine, an experienced veterinary technician then went into the cage with the dog to assess the situation. The dog stopped whining, which proves the dog was not dysphoric. Upon assessing the IV catheter, the veterinary technician noted the T-­port had become loose and the patient never received the pain medications. This example highlights two important things: 1) Biases (such as assuming the greyhounds are “just like that”) are dangerous and bad practices. 2) Good nursing care is very important. This scenario also highlights another point stated in this text, which is that the failure of one analgesic should not be the definitive rule-­ out of pain. Instead, we should offer a different analgesic with a different mechanism of action or consider dose adjustments when appropriate.

4.5 ­Dysphoria, Emergence Agitation, and Emergence Delirium Dysphoria associated with opioid administration is an emotional experience of intense discomfort or unease, sometimes with confusion and anxiety – not necessarily associated with an anesthetic event. Dysphoric patients are typically vocal, disruptive, agitated, and panicked. Truly dysphoric patients are inconsolable, meaning the patient does not respond to interaction. The dysphoric patient may also be bradycardic and disinterested in food or water, and the third eyelids may be visible. Dysphoria is ­typically associated with high dosages of opioid drugs and not typically seen at published dosages of single injection opioids unless that drug was given as a rapid bolus where transient ­dysphoria may occur. Painful patients typically will not become dysphoric even with large doses of opioids. Treatment of dysphoria can include a slow titration of naloxone to effect instead of boluses once commonly given (Hofmeister et al. 2006). Boluses can leave the patient in pain, causing stress and welfare concerns. The authors prefer to mix the calculated naloxone dose into sterile saline to be pushed over 5 minutes. When the animal begins to have a more positive effect, one stops with the slow infusion. Butorphanol, starting with a low dose, can also be used in the manner described above, yet it helps maintain at least mild analgesia. Both drugs have fast half-­ lives and may need to be repeated. Historically, sedatives may also be given to the patient, although this practice is somewhat contentious. Providing a sedative may compound the dysphoria via drug synergism or leave the animal in an anxious state but sedate. Medications like dexmedetomidine, where appropriate, may be preferable given its sedative and analgesic properties in addition to being fully reversible. Emergence agitation (EA) is very similar to opioid-­induced dysphoria, sharing many of the same symptoms but in addition can include thrashing, nonpurposeful movement, and the patient is typically inconsolable. However,

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EA is associated with awakening from general anesthesia and is typically transient. Some literature states EA is specifically associated with discomfort, pain, and anxiety. Treatment involves reassessment of the analgesics provided and considering the addition of more analgesics, potentially with some sedative qualities (Lee and Sung 2020). Emergence delirium (ED) echoes both dysphoria and emergence agitation in symptoms and is also associated with awakening after general anesthesia, but patients are typically consolable. ED may also manifest in hypoactive behavior or mixed hyperactive and hypoactive activities (Tolly et al. 2021). The relevance of these terms in this chapter is the difficulty in assessing pain in animals with any of the described conditions. The scenario of a patient having one of these conditions begs the question: What, then, should be administered? While each case is different, it is important to remember to provide some sort of analgesia. This is where slow infusions of dexmedetomidine prior to or even during recovery may be useful, or using oral doses of trazodone inserted rectally during recovery may help prevent or reduce these conditions (Jarosinski et al. 2021; O’Donnell et al. 2020).

4.6 ­Placebo, Caregiver Placebo, and Placebo-­by-­Proxy Placebo effects are highly complex and most often mentioned in human medicine regarding the clinical treatment of pain. Placebo effects are observable in animal studies and clinical presentations as well. While much more research is needed, the placebo-­by-­proxy effect may also occur in animal patients. This effect occurs when the patient is affected by the ­caregiver’s behavior toward a therapy, whether or not that treatment is objectively working (Grelotti and Kaptchuk 2011). Caregiver placebo is primarily noted in clinical research studies when owners or veterinary observers perceive an improvement in an

animal’s condition without treatment, such as giving a sugar pill. In a study from 2012, a ­caregiver placebo effect for owners evaluating their dog’s lameness occurred 39.7% of the time. In comparison, a caregiver placebo effect occurred 44.8% of the time when veterinarians examined dogs for lameness at a walk and trot, and 43.1% when veterinarians evaluated dogs for signs of pain on palpation of the joint. The effect was significantly enhanced with time despite mean ground reaction forces (GRFs) remaining unchanged for dogs during treatment with the placebo. Individually and objectively, of the 58 dogs in the study, 5 had GRFs that worsened by ≥5% over 42 days, 7  had GRFs that improved by ≥5% over 42 days, and 46  had GRFs that remained unchanged (Conzemius and Evans 2012). A 2017  literature review that identified five placebo-­controlled studies of analgesics in client-­owned cats with degenerative joint disease (DJD)-­associated pain showed an even higher caregiver placebo effect. Caregiver responses were analyzed using a clinical metrology instrument (CMI), Client Specific Outcome Measure (CSOM). Activity levels of the cats were assessed and categorized as “successes” or “failures” based on changes in CSOM score and activity counts from baseline. The caregiver placebo in this study was estimated between 50% and 70% of placebo-­treated cats, compared to 10–50% of cats classified as successes based on objectively measured activity. This study also showed that veterinary staff are slightly more susceptible to caregiver placebo. Both studies stress the importance of routinely utilizing clinical pain assessment tools (Gruen et al. 2017).

4.7 ­Non–species-­specific Assessments 4.7.1  Quantitative Sensory Testing (QST) QST is a noninvasive method to assess and quantify an individual’s sensory nerve function. This diagnostic tool is particularly useful

4.7 ­Non–species-­specific Assessments

in pain research and efficacy testing of new analgesic modalities. During QST, different stimuli (e.g. mechanical, vibration, thermal, or chemical) are applied to the skin using specific devices. For the mechanical QST technique, standardized von Frey filaments are often used to poke the skin without piercing it. Each sequential filament is increasingly rigid to determine the point at which the individual reacts to the filament. A von Frey filament is typically used on the underside of the animal paw. An autoalgometry device may be used similarly, but instead of a thin filament, a larger surface area probe is used to apply pressure to an appendage. A timed response to the filament or pressure probe is noted when the animal displays behaviors acknowledging the device by lifting the paw or attempting to move away. When a thermal stimulus is used, the technique is like the methods described above, but an area of a defined space or probe is heated to a specific temperature where reaction times are then recorded. Chemical QST stimulation is performed by applying or injecting a compound that causes nociception. Again, reaction times and behaviors are noted with and without an analgesic modality to compare outcomes (Mücke et al. 2021; Eckert et al. 2017).

4.7.2  Temporal Summation (TS) Temporal summation refers to an assessment where repeated or sustained stimuli, like the methods used in QST, can lead to an increased or cumulative response, particularly in the context of the nervous system. Regarding pain perception and the nervous system, temporal summation describes the increased pain perception or wind-­up effect with repeated or sustained noxious stimuli over time (Eckert et al. 2017).

4.7.3  Nociceptive Withdrawal Reflex (NWR) The nociceptive withdrawal reflex provides information about the function of the sensory system and central sensitization of dogs and

cats by analyzing the electromyographic (EMG) response of a peripheral nerve to an electrical or mechanical stimulation. The advantage of NWR is that it is noninvasive, and when compared with QST, NWR provides an objective measure (Lascelles et al. 2019).

4.7.4  Gait Analysis Another means of gauging a patient’s discomfort is gait analysis. Gait analysis computes the strength or pressure each limb produces during a gait cycle (Monteiro 2020). The most utilized gait analysis in clinical research and assessment centers are force plates and pressure-­sensitivity walkways. Both use GRFs to measure body weight, force, velocity, and acceleration (Lascelles et al. 2019). This is done by walking the animal in a straight line over a plate on the ground while maintaining the same trotting pace. Every time a limb contacts the plate, GRFs are measured. All data is analyzed on a computer connected to the plate. The information collected shows the musculoskeletal status of the patient to help diagnose and monitor limb lameness (Millis and Ciuperca 2015). While this analysis can be useful, it is also nuanced, particularly for animals that may have acclimated to an abnormal gait and have not received physical rehabilitation. When using only gait analysis, one may inadvertently misdiagnose an animal as still being “painful” because of an altered gaits secondary to muscle memory. This can be corrected by incorporating physical rehabilitation.

4.7.5  Pain Biomarkers Biomarkers have become a widely utilized tool in veterinary medicine employed for a range of purposes including assessing the health status of animals, diagnosing, and predicting diseases, and monitoring responses to treatments. The surge in technological advancements has led to a significant increase in both the variety and quantity of potential biomarkers, as reported in scientific literature and used in

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clinical and nonclinical settings. However, despite their widespread application, there is a notable lack of comprehensive reviews focusing on biomarkers specifically for pain in veterinary species. Currently, we are still in the infancy stages of validated biomarkers for assessing pain in animals. There is some promising research looking at potential pain biomarkers such as C-­Reactive Protein, Bradykinin 1–5 (Fernández et al. 2023), salivary microRNA in pigs, serum, and blood microRNAs in bovids, serum microRNA in horses, and plasma microRNAs in slider turtles (presented by Dr. Daniel Barratt, Pain in Animals Workshop, 2023), substance P, and various hormones like salivary cortisol in humans (de Bakker et al. 2021).

4.7.6  Machine Learning and Artificial Intelligence (AI) The incorporation of automated technologies in various aspects of veterinary care is on the rise. This includes the application of machine vision, which combines image capture devices with artificial intelligence (AI) methods and those in the machine learning framework. The evaluation of pain in animals presents significant challenges, making machine learning approaches particularly appealing for pain assessment. These methods provide noninvasive, continuous monitoring that does not stress the animals, enabling ongoing analysis of treatment progress or serving as an early diagnostic tool by promptly alerting veterinary staff to potential issues. Automated systems for assessing pain have been explored in a range of species, including mice, sheep, cats, rabbits, and even humans. Recent research has delved into the complexities involved in detecting pain using AI and machine learning, most prominently in horses. Validation is still underway in using AI and machine learning but is expected to be an acceptable method of pain evaluation in herd species in the very near future (Ollagnier et al. 2023; Lencioni et al. 2021; Pessanha et al. 2023). Another system using software called PainFace has been used to more accurately

detect facial grimaces of black mice on a scale from 0 to 8. PainFace can produce more than a hundred times the Mouse Grimace Scale data compared to human evaluators, and at a much faster rate (Zylka et  al.  2022). Most recently, Steagall et al. (2023) utilized advanced neural networks and machine learning algorithms to estimate the positions of facial landmarks and pain levels in cats, based on the Feline Grimace Scale© (FGS). The study involved annotating 3447 cat facial images with 37 distinct landmarks. Through training, various convolutional neural networks were evaluated for their efficiency, size, speed of prediction, accuracy, and compatibility with smartphone technology. A total of 35 geometric descriptors were formulated. The models demonstrated remarkable predictive abilities and accuracy in differentiating between cats in pain and those not in pain. This groundbreaking technology paved the way for creating an automated, smartphone-­ based application for assessing acute pain in cats and hopefully soon other species.

4.7.7  Activity Monitors (AMs) Like exercise trackers in humans, activity monitoring employs an accelerometer device attached to the collar of the dog or cat being assessed to record its activity levels by measuring changes in acceleration (Lascelles et  al.  2019; Monteiro et  al.  2022). Research shows that activity monitors can determine increased or decreased activity in response to treatment, suggesting improvements or declines (Lascelles et al. 2019). The advantage of this tool is the easy application and evaluation of a patient’s movements. Comparing trends over time, veterinary personnel can identify if there are alterations in activity. For instance, an increase in motor activity post-­ treatment with analgesics indicates an improvement in comfort, thus suggesting that the therapy is beneficial. One disadvantage is the lack of patient differentiation from a healthy vs. ailed patient or even species (Monteiro et al. 2022). Moreover, this is true as

4.8 ClinicalPainScoring ools Canineand Felinee

no two animals of the same species or breed are driven by equal energy. For example, a calm golden retriever sits or lays down near its owner while they watch TV, versus a highly rambunctious retriever that is constantly active while their owner is sedentary. This does not mean the calm canine is painful and the active one is not. Instead, it proves it can only be applied for comparing activity levels within the individual. Other concerns with AMs at this point are the lack of universal standard operating procedures and even FDA regulation of these devices. We don’t have a published approach for statistical evaluation of the data collected to assess validation or efficacy.

4.7.8  Facial Expression or Grimace Scales The development of grimace scales has escalated in interest over the last decade, but initial research started in the 1980s. Our understanding and refining of interpreting various species’ facial expressions has also evolved significantly and has melded with artificial intelligence potentially fine-­tuning the coding of various facial expressions. There are some limitations to using solely the grimace scales such as duration of grimace, assessor training, effects from various medications and social housing of the animal. Two of the most important limitations include stressors to the animal, outside of pain and unwanted social interaction  – essentially, the person assessing an animal may cause facial expressions that can be interpreted as pain. Despite these limitations, the advent of machine learning and artificial intelligence may help further develop facial scoring tools and eliminate some of the human interpreter related limitations. The most rigorously validated grimace scale is the one developed for cats, which is also now validated for use in kittens (Steagall et  al.  2023; Cheng et  al.  2023). So far, facial expressions or grimace scales have been published for several species, including cats, mice, rats, horses, pigs, rabbits, sheep, cows, ferrets, and a seal (Mogil et al. 2020, Sotocinal et al. 2011).

4.8 ­Clinical Pain Scoring Tools (Canine and Feline) In nonverbal patients like animals, we rely more heavily on behavioral signs as the backbone for recognizing and assessing pain (Table 4.1). In contrast, previously, we relied almost solely on vital signs such as heart rate, respiratory rate, blood pressure, and temperature. Our knowledge of the expected severity and cause of pain should also help guide the clinical management of pain. However, we must also be careful not to underestimate the discomfort of a procedure or trauma that can cause discomfort, as everyone’s pain experience is unique. Instead, we should error on the side of caution by applying analgesic strategies (pharmaceuticals, supplements, physical modalities) and possibly anxiolytics if even the slightest discomfort may occur. This section describes the various assessment tools, known as CMIs and client-­reported outcome measures (CROMs), more broadly termed pain scoring tools, currently available and some prospects currently underway. In chronic or palliative care cases, typical pain-­scoring tools are best used with quality of life (QoL) or health-­ related quality of life tools (HRQoL). Unfortunately, there are no pain-­scoring tools for most species. This is where the adoption of a system for assessing any animal is helpful (Figures 4.2–4.5). A systematic assessment will consider the potential etiology of pain, the species’ ­natural behaviors, and potentially their vital signs. When available the authors recommend adopting pain-­scoring tools for consistency within a practice, with preference for those that are considered validated when possible (Table 4.2). Pain assessments should also be made at 4-­ to 6-­hour intervals throughout hospitalization in the general patient population and much more frequently in the critical care setting where patient status is more dynamic. In this chapter, we highlight some of the more common pain-­ scoring tools. When an animal is ready to go home or is in chronic pain, client education is crucial to maintaining appropriate care. Many

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Table 4.1  Common pain behaviors in companion animals. Symptom

Dog

Cat

Vocalizing

Yes

Yes

Social behavior

Decreased

Will become solitary, reclusive

Restlessness

Yes

Possibly but more often its reduced activity, seclusion

Abnormal posturing

Yes; also reluctance to lie down or get up

Yes; reluctance to get up

Increased temp

Possibly

Possibly

Inappetence

Yes

Yes

Increased BP

Possibly

Possibly

Aggression

Yes

Yes

Frequent movement (weight shifting)

Yes, especially for OA

No

Facial expression

Yes, fixed stares, depressed

Yes, depressed facial expressions, squinted eyes, furrowed brows

Trembling

Yes

Yes

Depression

Yes – dull

Yes

Anxiety

Yes

Yes

Self-­grooming

Self-­mutilation

Unkempt

Papillary enlargement

Yes

Yes

Licking/chewing/staring at site

Yes

Yes

Respiration

Tachypnea

Tachypnea/open mouth panting

Tail carriage

Tucked down

Tail flicking but could also be anger

Inappropriate urination

Yes

Yes

Eyes

May be dilated and may move instead of head or neck

May be dilated, also squinting

Heart rate/rhythm

May have tachycardia but can be from other events; also pain can cause VPCs

May have tachycardia but can be from other events; also pain can cause VPCs

Facial expressions

Fixed stare or head down depressed

Furrowed brows

Hair coat

Hair loss/thin coat

Unkempt

of the tools described can be easily taught to clients to better assess their animal at home (Lascelles et al. 2019; Monteiro et al. 2022).

4.8.1  Canine Acute Pain Scoring 4.8.1.1  Glasgow Composite Measure Pain Scale – Short and Long Forms (CMPS) (Validated)

The CMPS-­SF (short-­form composite measure pain score) is a swift and reliable tool for clinical use, specifically designed to assist in

clinical decision-­making for dogs experiencing acute pain. This tool encompasses 30 descriptive options across six behavioral categories, including mobility. In each category, the descriptors are arranged in a numerical order based on their associated level of pain severity. The assessor selects the descriptor that most accurately reflects the dog’s behavior or condition in each category. Adherence to the outlined assessment protocol, as detailed in the questionnaire, is crucial for

4.8 ClinicalPainScoring ools Canineand Felinee

Table 4.2  A list of canine and feline pain assessment tools. Species

Pain assessment tool name

Tool acronym

Type of pain

Validation

Dogs

Dynamic and interactive Visual Analogue Scale

DIVAS

Acute

Not validated

University of Melbourne Pain Scale

Melbourne

Acute

Not validated

Glasgow Composite Pain Scale

GCPS

Acute

Validated

4AVET-­Pain Scale

4AVET-­Pain Scale

Acute

Not validated

Cincinnati Orthopedic Disability Index

CODI

Chronic orthopedic

Not validated

Composite measure pain scale

CMPS

Acute

Validated

Health related quality of life instruments (Vetmetrica)

HRQL instruments

Chronic

Validated

Short Form – Glasgow Composite Pain Scale

SF-­GCPS

Acute

Validated

Cats

Canine Brief Pain Inventory

CBPI

Chronic

Validated

Helsinki Chronic Pain Index

HCPI

Chronic

Validated (in Finnish)

Liverpool Osteoarthritis in Dogs

LOAD

Chronic

Validated

Colorado State University Canine Acute Pain (educational tool)

CSU-­CAP

Acute

Not validated

Short Form – Health related quality of life instruments (Vetmetrica)

Short Form – HRQL instr.

Chronic

Not validated

Canine Osteoarthritis Staging Tool

COAST

Chronic

Validated

JSSAP Canine Chronic Pain Index

JSSAP

Chronic

Not validated

Composite oral and maxillofacial pain scale – canine/feline

COPS-­C/F

Acute and chronic oral and facial

Initial validation

Canine Post Amputation Pain scale

CAMPPAIN

Chronic post amputation pain

Not validated

Milan Pet Quality of Life

MPQL

Quality of life

Not validated

AAHA Owner Assessment

AAHA-­Cital

Acute and chronic

Not validated

Colorado State University Feline Acute Pain Scale

CSU-­FAPS

Acute

Initial validation

Client Specific Outcome Measures

CSOM

Osteoarthritis

Validated

UNESP-­Botucatu-­MCPS

UNESP-­ Botucatu-­MCPS

Acute

Validated

Feline Musculoskeletal Pain Index

FMPI

Chronic

Not validated

Glasgow Composite measure pain scale

CMPS-­Feline

Acute

Validated (Continued)

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Table 4.2  (Continued) Species

Pain assessment tool name

Tool acronym

Type of pain

Validation

Montreal instrument for cat arthritis testing (for veterinarians)

MI-­CAT(V)

Arthritis

Not validated

Montreal instrument for cat arthritis testing (for caretakers)

MI-­CAT(C)

Arthritis

Initial validation

Feline Grimace Scale

FGS

Acute

Validated

Health related quality of life instruments (Vetmetrica)

HRQL instruments

Chronic

Initial validation

Composite oral and maxillofacial pain scale – canine/feline

COPS-­C/F

Acute and chronic

Initial validation

Small animal algometer

SMALGO tool

Chronic gingivostomatitis

Not validated

Short Form of the Feline Musculoskeletal Pain Index

SF-­FMPI

Chronic

Not validated

AAHA Owner

AAHA-­Cital

Acute & Chronic

Not validated

by summing the ranked scores from each category. The highest possible score is 24, which reduces to 20  when mobility cannot be assessed. The total score obtained from CMPS-­SF has proven to be a valuable indicator of the need for analgesic intervention, with the recommended threshold for analgesic action being a score of 6 out of 24, or 5 out of 20 when mobility assessment is not possible. More information about this tool can be found at the Newmetrica website dedicated to  acute pain measurement: http://www. newmetrica.com/acute-­p ain-­m easurement (Holton et al. 2001; Morton et al. 2005). 4.8.1.2  French Association for Animal Anesthesia and Analgesia Pain Scoring System (4A-­Vet) (Validated)

The 4A-­VET system is effective in differentiating pain intensity in dogs for acute orthopedic pain, but bias is introduced with the sedative side effects related to some analgesics (Rialland et al. 2012). 4.8.1.3  University of Melbourne Pain Scale (UMPS) (Validated)

The University of Melbourne pain scale ­comprises a blend of behavior-­oriented

questions and evaluations of physiological parameters. This scale is practically designed for clinical application, particularly with dogs. However, it has certain drawbacks, such as the incorporation of physiological measurements, an absence of content validation, and no clear guidelines regarding points for initiating analgesic treatment (Hernandez-­Avalos et al. 2019; Monteiro et al. 2022).

4.8.2  Canine Chronic Pain Scoring 4.8.2.1  Canine Brief Pain Inventory (CBPI) (Validated)

The CBPI was initially developed to mimic the human brief pain inventory (BPI) and validated as the Canine BPI (Cleeland and Ryan 1994; Brown et al. 2013). It is an owner-­ completed questionnaire with 11 queries to monitor chronic pain in dogs with chronic osteoarthritis (OA). Questions 1–4 pertain to the perceived intensity of pain. A scale of 0–10 is used to score each item, where 0 is no pain and 10 is extreme pain. Then, an average is calculated based on the responses from the first four items to determine the patient’s intensity score of perceived pain. The next six questions (5–10) relate to changes in the dog’s daily

4.8 ClinicalPainScoring ools Canineand Felinee

activities from the perceived pain, e.g. general activity, enjoyment of life, rising to stand, walking, running, and climbing. They, too, are scored on a scale of 0–10, where 0 has no interference, with 10 being complete interference. These values are then averaged to represent the pain interference score (Brown et al. 2013). In the initial study by Brown et  al.  2007, “Development and psychometric testing of an instrument design to measure chronic pain in dogs with osteoarthritis,” CBPI was completed by 50 owners with clinically normal dogs and 70 owners of dogs with OA. The study results showed normal dogs had an intensity or severity pain score range of 0–0.75 and an interference score range of 0–0.67, while dogs with OA had a severity pain score range of 1–7.75 and an interference score range of 1.5–9. The final question (11) is a single graded quality of life scoring based on the owner’s overall impression of the animal’s severity of pain, interference of pain, and quality of life over the past seven days, e.g. poor, fair, good, very good, or excellent. It is not used as part of the overall pain score but rather as a validation of the severity and interference scores (Brown et al. 2013). Scores can be useful to determine response to therapy for pain severity, functional impairment, and quality of life by comparing these results over time. 4.8.2.2  Helsinki Chronic Pain Index (HCPI) (Validated)

The HCPI is a questionnaire that is used to monitor chronic pain in dogs with OA yet has limited validation (Gruen et  al.  2022). It consists of 11 items, and the score is based on the owner’s evaluation of their dog’s behavior and ability to perform activities. The owner chooses one option from the five-­point descriptive scale. The selection is given each a numeric value from 0 to 4, divided between a simple descriptive scale (SDS) (demeanor and behavior and locomotion) and a VAS (pain and locomotion) (TVP 2013). The sum of all the values chosen provides a minimum index score of 0 (average healthy dog) to a maximum index score of 44 (very painful) (Piras

et  al.  2021). The HCPI can be used to assess response to therapy, meaning if a dog with OA is treated with a medication and the HCPI is used over time to monitor pain, a score lower than the original assessment means response to treatment, while the same or increased score represents no response to that medication. A significant limitation of the index is that it asks for information related to the status of the dog rather than the average status of the dog over time. This can result in a lack of sensitivity with a wide range of score variability depending on whether a dog is having a “good” or “bad” day. Averaging the index over a week may allow for more reliable results. Available at www.fourleg.com. 4.8.2.3  Liverpool Osteoarthritis in Dogs (LOAD) (Validated)

LOAD was originally developed to diagnose elbow OA. However, it has been extensively used and validated to measure chronic pain in dogs with OA (Gruen et  al.  2022). The questionnaire reviews 13 areas with five general and eight activity-­based domains. Answers are scored based on the owner’s assessment using a 0–4 descriptive scale, with 0 being healthy movements for the animal and 4  indicating severe disease. LOAD can be used to monitor response to therapy and has shown a correlation with force-­platform data in other studies (Alves et al. 2022).

4.8.3  Feline Acute Pain Scoring 4.8.3.1  Glasgow Composite Measure Pain Scale-­Short-­Form (CMPS-­SF) (Validated)

The CMPS-­Feline, introduced in early 2016, stands out as the inaugural tool incorporating both facial expressions and behavioral indicators to assess feline pain. It comprises six distinct items, each with its unique scoring range. The highest possible score is 24, but this reduces to 20  in cases where mobility assessment is not feasible. The threshold for considering rescue analgesia is set at a score of 6 or more out of 24, or 5 or more out of 20 in situations where mobility can’t be evaluated. More

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information about this tool can be found at the Newmetrica website dedicated to acute pain measurement: http://www.newmetrica.com/ acute-­pain-­measurement. 4.8.3.2  Feline Grimace Scale (FGS) (Validated)

The development of the FGS, now validated in kittens (Cheng et al. 2023), involved analyzing video footage of both painful and nonpainful cats, primarily those belonging to clients and presented at the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine at Université de Montréal. In cases where cats were assessed as experiencing pain, they were administered analgesics. Cat owners provided informed consent for their pets’ participation in the study. All treatments and care administered were conducted using methods that are friendly to cats, ensuring that no additional pain or harm was caused during the process. The FGS has an application for smartphones where owners can submit pictures of their cat for assessment and machine learning (Monteiro et al. 2022). See the training manual included in this text or at https://www.felinegrimacescale.com.

4.8.4  Feline Chronic Pain Scoring 4.8.4.1  Client-­specific Outcome Measures – Feline (CSOMf) (Validated)

The CSOMf is a questionnaire where owners identify three specific activities that their feline is impaired to perform (Gruen et al. 2015). The activities chosen should be challenging for the cat to perform. They are then rated by the owner using a Likert scale based on the level of difficulty within the last week. The Likert scale has five options, from no problem performing the activity to unable to perform the activity. Each option is given a numeric score, ranging from 0 to 4, where 0 is no problem, and 4 is impossible. This metrology was fashioned after the Cincinnati Orthopedic Disability Index and uses the subjective assessments of the owners as the central detector and monitor for

chronic pain in their cats with OA (Gruen et al. 2022). Research by Lascelles in 2007 supported the validation of the owners’ ability to assess their cat’s responses to treatments and the use of the CSOMf for more quantitative data in treating cats with chronic pain. Unfortunately, developing this instrument with the appropriate activities can be time-­ consuming for both client and veterinarian when comparing scores over time to assess response to therapy (Gruen et al. 2022). 4.8.4.2  Montreal Instrument for Cat Arthritis Testing-­caretaker (MI-­CAT-(c)) (Validated)

This instrument has been validated and is used by owners to assess and monitor treatment efficacy in cats with OA. The scale is composed of two tables. One table has 18  items separated into three categories: (i) agility, (ii) social/play/exploratory behaviors, and (iii) self-­maintenance. The other table has 20 items split into three categories: (i) agility, (ii) self-­ maintenance, and (iii) physical condition. Owners choose yes, no, or do not know/do not apply for each item. Responses are scored based on the number of abnormal responses divided by the total answers – meaning “no” in table one and “yes” in table two register as an abnormal response over the total number of responses. Scores are rated at 0–1, where poor is 35 is considered “acceptable.” The scale can be helpful in dogs and cats; however, it is essential to remember that the scale is not validated, and a total score of 35 or more is an arbitrary number that may not necessarily correlate with a true acceptable quality of life. Nonetheless, the scale allows owners to reflect on their pet’s quality of life and can be helpful for making difficult decisions in end-­of-­life care. The scale can be obtained here: http:// www.veterinarypracticenews.com/vet-­practice-­ newscolumns/bond-­b eyond/quality-­o f-­l ife-­ scale.aspx 4.8.4.7  VetMetrica™ Health-­related Quality of Life (HRQoL) (Validated)

This metrology tool is a structured questionnaire used to either monitor a specific chronic disease or the quality of life in a healthy or sick animal. Quality-­of-­life measurements often collect both casual and indicator variables. The indicators are casual (i.e. vomiting) because they affect quality of life. At the same time, variables like perceived energy are not associated with quality of life. However, this ­metrology reviews how the animal feels, with indicators measuring the emotional components using various domains, e.g. happiness or comfort. Two web-­based HRQoL generic questionnaires are available, one for dog owners and one for cat owners (Davies et al. 2021). The canine HRQoL instrument is validated and generates scores via 22  items from the following four domains: energy, happiness, comfort, and calmness.

4.9 ­Bovid

In contrast, the feline HRQoL is moderately validated, with only 20  items from 3 domains: vitality, comfort, and emotional well-­being. All domains were derived using a multivariate statistical analysis (Davies et al. 2021). Like other metrologies, each item is scored on a Likert scale with seven options for owners to choose from, where 0 is equivalent to “could not be less” and 6 means “could not be more” (Davies et al. 2021). The main advantages to the VetMetrica HRQoL tool include easy online access as well as its varied application for monitoring routine wellness, disease progression, end-­of-­life decisions, and drug trial outcome measures based on individual treatment responses. It provides real-­time data collection and communications through a VetSupport+ platform or PetDialog™ via most smartphone providers. Reminders, push notifications, and quick access for both the client and the veterinarian are available. Unfortunately, the utility of this metrology varies based on the interpretation of the results as well as the consistency of information input (Figures 4.2 to 4.4). 4.8.4.8  Food and Fiber Species Pain Recognition and Scoring

The following animal species are included in this group: cattle, sheep and goats, and pigs. A comprehensive review was recently published focused on evaluating the effectiveness of pain assessment tools used for farm animals. The study adhered to the PRISMA guidelines and was preceded by a protocol published in the same journal. The research included studies that aimed to develop validated tools for assessing both acute and chronic pain in farm animals, emphasizing behavioral and facial indicators. The researchers independently conducted data collection and analysis, following the COSMIN (Consensus-­based Standards for the Selection of Health Measurement Instruments) guidelines. The evaluation encompassed nine areas: two related to the creation of the scale (overall design and content validity) and seven linked to its measurement attributes (consistency, reliability, error margin, criterion and construct validity,

adaptability, and cross-­cultural relevance). Each tool’s credibility was rated (high, moderate, low, or very low) based on factors like methodological soundness, the quantity of studies, and the outcomes of these studies. The review covered 20 tools for bovids, sheep, and swine, noting significant differences in their development and measurement qualities. Three tools based on behavior analysis received a high rating: the UCAPS (Unesp-­Botucatu Unidimensional Composite Pain Scale for cattle post-­surgery pain assessment), USAPS (Unesp-­ Botucatu Sheep Acute Composite Pain Scale), and UPAPS (Unesp-­Botucatu Pig Composite Acute Pain Scale). Four others received a moderate rating: the MPSS (Multidimensional Pain Scoring System for bovines), SPFES (Sheep Pain Facial Expression Scale), LGS (Lamb Grimace Scale), and PGS-­B (Piglet Grimace Scale-­B). The majority, 13 in total, were rated low or very low in overall evidence. Construct validity emerged as the most frequently reported attribute, followed by criterion validity and reliability. The study highlighted an urgent need for validated tools to assess pain in buffalos, goats, camelids, and birds (Tomacheuski et al. 2023).

4.9 ­Bovids Cattle in pain often appear dull and depressed, with the head held low and showing little interest in their surroundings. Symptoms include inappetence, weight loss, and, in milking cows, a sudden drop in milk yield. Severe pain often results in rapid shallow respirations. On being handled, cows may react violently or adopt a rigid posture designed to immobilize the painful region. Grunting and grinding of the teeth may be heard. Acute pain may be associated with bellowing. Generally, signs of abdominal pain are like those seen in the horse but are less marked. Rigid posture may lead to a lack of grooming due to unwillingness to turn the neck. In acute abdominal conditions, such as intestinal strangulation, the animal adopts a characteristic stance with one hindfoot placed directly in front of the other (Figure 4.6).

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Figure 4.2  AAHA/Cital in Home Pain Assessment (Feline) (nonvalidated). This pain assessment tool is designed using the CSU, FGS and other validated pain scoring systems to help pet owners identify acute and chronic pain. Source: Available at: aaha.org.

4.9 ­Bovid

Figure 4.3  The short form composite measure pain score (CMPS-­SF). Source: Available at: https://wsava. org/wp-­content/uploads/2020/01/Canine-­CMPS-­SF.pdf.

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Figure 4.4  (a–d) Feline grimace scale training manual. Source: Springer Nature / ‘https://www. felinegrimacescale.com/about / last accessed Feb 21, 2024.

4.9 ­Bovid

Figure 4.4  (Continued)

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Figure 4.4  (Continued)

4.9 ­Bovid

Figure 4.4  (Continued)

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Figure 4.5  CSU canine acute pain scale (nonvalidated). Source: Colorado State University / https:// vetmedbiosci.colostate.edu/vth/wp-content/uploads/sites/7/2020/12/canine-pain-scale.pdf / last accessed Feb 21, 2024.

4.10 SmallRuminantsand Camelids ●●

●●

●●

●●

●●

Figure 4.6  Bovine pain stance. Source: Courtesy of Mark Brinker. ●● ●●

Localized pain may be indicated by persistent licking of an area of skin or kicking at the offending area (Figure  4.6). Bovine orbital tightening or ear position may be an indication of pain and should be pursued (Millman 2013). Cows with moderate clinical mastitis can exhibit an increased heart rate, temperature, and respiratory rate (Leslie and Petersson-Wolfe 2012). Cortisol levels were increased as well as increased “hock-­to-­hock” distances indicating an altered stance (Milne et al. 2003). Mastitis cows also have an increased mechanical pressure sensitivity on the leg that is closest to the infected mammary quarter, suggesting a change in pain information processing because of inflammation (Leslie and Petersson-Wolfe 2012). A gait locomotion scoring system has been published and found to be sensitive to identify cows with severe hoof lesions as well as lame cows that were provided with a local anesthetic (Figure  4.7) (von Keyserlingk et al. 2009; Flower et al. 2006; Millman 2013).

4.9.1  Indications of Pain in Cattle ●● ●●

Decreased movement/locomotion Decreased interaction with other animals in the group

●● ●● ●● ●● ●●

Decreased feed intake (e.g. “hollow” left flank caused by an empty rumen) Changes relevant to the source of the pain being experienced (e.g. altered locomotion, flank watching or kicking, or ear twitching) Level of mental activity/responsiveness (animals in severe pain often show reduced responsiveness to stimuli) Changes in normal postures associated with pain (e.g. lateral recumbency, standing motionless, or drooping of the ears) Easily measurable indicators of physiological stress (e.g. increased heart rate, increased pupil size, altered rate and depth of respiration, or trembling) Bruxism (tooth grinding) Poor coat condition (e.g. rough, dusty, or unkempt) caused by decreased grooming Dropped head Tension of the muscles above the eyes Ears are tense, low, and facing backward Tension of lateral facial muscles Strained and dilated nostrils, tonus of the lips

4.10 ­Small Ruminants and Camelids Small ruminants, like sheep and goats, and camelids are prey species that often only show subtle signs of pain (Galatos 2011) (Figure  4.8). Goats will often bleat, while sheep may only exhibit tachypnea, inappetence, grinding of teeth, immobility, or abnormal gait (Hall et al. 2001; Smith et  al.  2021). Following procedures such as castration and tail docking, lambs may show signs of discomfort such as standing up and lying down repeatedly, tail wagging, occasional bleating, neck extension, dorsal lip curling, kicking, rolling, and hyperventilation. Other subtle changes in behavior may be noticed such as changes in appetite, urination, defection, and social interaction (Smith et al. 2021).

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Figure 4.7  Locomotion scoring of dairy cows. Source: Adapted from: Dahhan et al. (2021).

4.12 EquidPainRecognitionand Scoring Moderate (1)

Severe (2)

Not present (0)

Moderate (1)

Severe (3)

Flehming

Ear & head position

Orbital tightening

Not present (0)

Figure 4.8  Action units of the sheep grimace scale (SGS). Source: Häger et al. (2017) / PUBLIC LIBRARY OF SCIENCE (PLOS) / CC BY 4.0.

4.11 ­Swine

●● ●●

When swine react differently from their typical behavioral patterns, pain, and distress might be the cause (Bollen et al. 2000). Pigs in pain may show changes in gait and posture. They normally squeal and attempt to escape when handled; however, these reactions may be heightened when the animal is in pain. Adult pigs may become aggressive. Squealing is also characteristic when painful areas are palpated. Handling of chronic lesions may not elicit signs of pain. Pigs will often be unwilling to move and may hide in bedding if possible (Ison et al. 2016).

4.11.1  Normal Behavioral Observations in Swine ●● ●● ●●

Interest in the surroundings, including staff Willingness to move around Explorative behavior

●● ●●

Tail wagging Reaction to handling Vocalization when presented with feed Willingness to eat

4.12 ­Equid Pain Recognition and Scoring Pain can manifest itself by producing changes in an equid’s physiology, behavior, and emotional state. Some of these changes can be subtle, and discussing the animal’s behavior with its primary caregiver can be beneficial since they are most familiar with the animal. The pain experience can also be affected by the animal’s psychological state when nociception occurs. Studies have shown that during periods of extreme stress or fear, pain can be suppressed by the animal’s body  – stress-­ induced analgesia. This phenomenon is part

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of  the “fight-­or-­flight response,” in which the sympathetic nervous system is engaged and endogenous catecholamines are released; the state of fear takes over, and pain is inhibited during that time. On the opposite end of this spectrum is the phenomenon of “stress-­ induced hyperalgesia,” in which animals experiencing extreme anxiety can have an increased perception of pain (Van Loon et  al. 2010). There are indications that horses and humans experience pain in a similar manner and that horses do exhibit emotional responses to pain as well.

4.12.1  Horses Pain in the horse is like other species, a multidimensional experience. Pain can be exhibited through changes in behavior, emotion, or physiologic parameters (DeGouff 2010). These changes can be difficult to assess, and therefore, the recognition of equine pain remains subjective. Recognition and treatment of pain is essential in providing the individual with a good quality of life. Horses are considered prey animals, and it is therefore part of their instinct to hide pain as much as possible to protect themselves (Lockhead 2010). Signs of pain in the horse can initially be subtle but can become obvious when they can no longer hide it due to its severity. Signs of pain can also vary based on the horse’s age, breed, temperament, and specific disease. Some horses such as draft horses are much more stoic than other breeds even in the face of severe pain. “Hot-­blooded” breeds like Arabians and Thoroughbreds are more likely to show signs of pain, as are young horses and foals. When horses are in unfamiliar environments, such as the hospital, pain can be masked (stress-­induced analgesia). Some basic physiologic responses should be assessed when trying to gauge the level of pain in an individual. These include behavior/attitude, activity level, overall appearance, appetite, posture, facial expressions, interaction with people and/or other horses, willingness

to work, and response to being handled. Sometimes, the behaviors associated with pain can be nonspecific or correlate with a specific location such as the abdomen, limb, foot, head, mouth, or castration site (Lerche  2009). The most common types of pain in the horse include orthopedic pain and abdominal/ colic pain. Orthopedic pain typically presents as a lameness and can include pain in the joints, tendon/ligaments, long bones, and back pain. Lameness is a result of the horse trying to avoid the painful area by compensating on the other limbs (Keegan 2007). Overload of the compensating limb can cause “support limb laminitis” secondary to the original lameness (Mitchell et al. 2014). 4.12.1.1  Appearance of the Normal Horse

The equine species has an intricate and expressive language; they are herd-­based, social creatures with a specific hierarchy, which makes effective communication necessary. In addition to facial expressions and posture/position, the horse has many vocalizations used to express themselves. Equine vocalizations can be classified as neigh, whinny, nicker, squeals, snorts, and even roars. The normal, healthy equine should demonstrate these traits ●● ●●

●● ●●

●● ●● ●● ●● ●● ●●

●● ●●

Alert mental state Appropriate response to stimulus (not dull or unresponsive) Good appetite Able to chew and swallow normally and does not “drop feed” Urinates normally, with normal color Defecates normally, with formed manure Normal respiratory rate and pattern Normal heart rate and rhythm Normal rectal temperature Ambulates normally, weight bearing on all four limbs Performs work normally Interacts with people and other horses normally

4.12 EquidPainRecognitionand Scoring

4.12.1.2  Somatic Pain Indicators ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●●

Abnormal weight distribution Mild to severe lameness Guarding of a limb Weight shifting between limbs Pointing, hanging, or rotating of the limbs Reluctance to move Sensitivity response to palpation of painful area Pain after limb flexion testing Sensitivity to hoof tester application Recumbency Change in appetite

4.12.1.3  Signs of Laminitis Pain Vary with the Progression of the Disease ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●●

Rocking or shifting weight to rear feet Anxiety Muscle fasciculation Sweating Lameness at the walk Reluctant to lift a forelimb Reluctant to walk at later stage Decreased appetite Stands at the back of stall Increased digital pulses Camped-­out stance Increased heart and/or respiratory rate Refusal to move or recumbency

4.12.1.4  Visceral Pain Indicators ●● ●●

●● ●● ●● ●●

●● ●● ●● ●● ●● ●● ●●

Depressed/dull appearance (chronic pain) Restlessness, anxiety, or agitation (acute pain) Flank watching Fixed stare and dilated nostrils Lowered head carriage Aggression (toward handlers, horses, or its own foal) Limited to no interaction with people Standing at back of stall Stretching/“parking out” Decreased appetite and food pocketing Groaning/grunting Rigid/reluctance to move Kicking at abdomen

●● ●● ●● ●●

●●

●● ●●

Recumbency Rolling Increased heart rate Increased respiratory rate, typically shallow Violently throwing itself down (severe colic) Abdominal distension Little to no gut sounds on auscultation

4.12.1.5  Horse Grimace Scale

This scale, like other species, uses facial expressions to recognize painful behavior in horses. Six facial actions were defined in the scale: stiffly backward ears, orbital tightening, tension above the eyes, strained chewing muscles, mouth strain, and a pronounced chin and strained nostrils. During the development of this scale, the greatest pain was seen 8 hours after an operation when in most cases analgesics have worn off (Dalla Costa et al. 2014). It was noted that darker-­colored horses were harder to score than lighter-­ colored ones. Many factors must be considered when using a pain scoring system in the horse, and there is no one standardized pain scale for the horse (Figure 4.9). In most cases, pain is assessed in a basic format such as mild, moderate, and severe. A horse exhibiting mild pain may be prescribed an NSAID, whereas a horse suffering from extreme pain needs significant analgesia that may require hospitalization (Lerche  2009). A few composite pain scales (CPS) have been used for horses in clinical practice. In 2008, a CPS was developed for orthopedic pain in horses by Bussières et  al., which incorporated a numerical system that considered many different factors including the horse’s response to stimuli, physiologic parameters, and spontaneous behavior. The score range for this scale is from 0, which is no sign of pain, all the way through 39 for the maximum pain. Some of the data recorded included behavioral changes such as overall appearance, posture, head or ear movement, pawing,

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4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species Orbital tightening

Stiffly backwards ears

Not present (0)

Moderately present (1)

Obviously present (2)

The ears are held stiffly and turned backwards. As a result, the space between the ears may appear wider relative to baseline. Tension above the eye area

Not present (0)

Moderately present (1)

Obviously present (2)

The contraction of the muscles in the area above the eye causes the increased visibility of the underlying bone surfaces. If temporal crest bone is clearly visible should be coded as “obviously present” or “2”. Mouth strained and pronounced chin

Not present Moderately Obviously (0) present (1) present (2) Strained mouth is clearly visible when upper lip is drawn back and lower lip causes a pronounced “chin”.

Not present Moderately Obviously (0) present (1) present (2) The eyelid is partially or completely closed. Any eyelid closure that reduces the eye size by more than half should be coded as “obviously present” or “2”. Prominent strained chewing muscles

Not present Moderately Obviously (0) present (1) present (2) Straining chewing muscles are clearly visible as an increase tension above the mouth. If chewing muscles are clearly prominent and recognizable the score should be coded as “obviously present” or “2”. Strained nostrils and flattening of the profile

Not present (0)

Moderately present (1)

Obviously present (2)

Nostrils look strained and slightly dilated, the profile of the nose flattens and lips elongate.

Figure 4.9  Horse grimace pain scale (HGS). Source: Dalla Costa et al. (2014) / PUBLIC LIBRARY OF SCIENCE (PLOS) / CC BY 4.0.

kicking at abdomen, sweating, appetite, how the horse responds to people/interaction, and how the horse responds to stimulation of the painful area. The physiologic parameters

included heart rate, respiratory rate, GI sounds, and temperature (Wagner  2010). These variables can be used to assess horses experiencing ­visceral pain as well (DeGouff 2010).

4.13 ExoticSpeciesPainRecognitionand Scoring

Table 4.3  AAEP lameness grading system. Lameness grade

Definition

0

No lameness under any circumstances

1

Lameness difficult to observe, inconsistent regardless of circumstance

2

Difficult to observe at walk and trot in straight line but apparent while carrying weight, on a circle, inclines, or hard surfaces

3

Consistently observable at the trot under all circumstances

4

Obvious lameness at the walk

5

Lameness produces minimal weight bearing in motion, at rest or has complete inability to move

components to better assess these patients (Van Loon 2012) (Table 4.4). There are other types of pain scoring systems devoted to assessing abdominal/colic pain, wound sensitivity, and others. The desire and effort in attempting to gain further knowledge about equine pain response is continuing to increase. Over time, this will help improve pain recognition and overall pain management in this species.

4.12.2  Donkeys The Donkey Pain Scale (DOPS) is the only pain assessment tool for donkeys specifically designed for acute postoperative pain (Table  4.5). It is important to note that ­donkeys and horses are different behaviorally and extrapolation from either is fraught with nuances (Oliveira et al. 2021).

Source: Wagner (2010) / with permission of Elsevier.

Regarding assessing lameness in the horse, the American Association of Equine Practitioners (AAEP) developed a grade system that is widely used among equine practitioners; this scale ranges from 0 to 5 (Table 4.3). There is a verbal rating scale, using A–F, which is fairly similar to the AAEP’s system. Lameness can also be assessed using force plate gait analysis, though there are variations in results based on breeds, and the force plate itself is not available to most practices (Van Loon 2012). Laminitis is one of the most agonizingly painful lameness syndromes in the horse. To attempt to provide appropriate analgesia to these patients, Niles Obel developed the Obel Laminitis Pain Scale (Menzies-­Gow et al. 2010). There was also a modified composite pain scoring system developed that included the Obel pain scale and a NRS describing ­multifactorial behavioral and physiological

4.13 ­Exotic Species Pain Recognition and Scoring 4.13.1  Birds Since Dr. Pepperburg’s studies in the 1970s, birds have escaped, to an extent, the archaic stereotype of beings that only follow instincts and have been recognized as true cognitive, sentient animals. It is now understood that they have the anatomical and physiological capacity for stimuli to be “sensed” or felt, transmitted to the brain, and interpreted as pain. This diverse class of animals may present to the veterinary clinic as a pet bird, production animal, zoo animal, or wildlife. The presentation of a bird patient may also be varied in age, gender, and socialization with both people and conspecifics. All of this may affect the normal behavior expected and how pain may be observed. Stress can alter normal behavior and even mask pain-­associated behaviors.

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Table 4.4  Pain scoring system for laminitis. Modified composite pain score Dynamic score: modified Obel grading system Grade descriptor 1)  Frequent shifting of weight between the feet with no discernible lameness at the walk 2)  Does not resist having a foreleg lifted, is not reluctant to walk, but does show lameness at the walk 3)  Resists having a foreleg lifted and is reluctant to walk 4)  Walks only if forced Static score: modified from Glasgow composite scale Score descriptor 1)  No pain or distress: normal behavior 2)  Mild pain: irritable, restless, decreased appetite 3)  Mild pain: 2 plus resists handling 4)  Mild–moderate pain: 3 plus standing in back of stall or with back to stall door 5)  Moderate pain: 4 plus camped-­out legs, increased digital pulses 6)  Moderate–severe pain: 5 plus frequent recumbency, HR > 44 beats/min, and/or RR > 24 breaths/min 7)  Moderate–severe pain: 6 plus sweating, muscle fasciculation, head tossing 8)  Severe pain: 7 plus unwilling to move 9)  Severe–extreme pain: 8 plus not weight bearing when standing 10)  Extreme pain: 9 or entirely recumbent, bordering on agonal Maximum possible score: 14 Source: Adapted from Driessen et al. (2010).

4.13.2  Appearance of a Non-­painful Bird

4.13.3  Appearance of a Painful Bird

To best assess an avian patient, one must be familiar with that species and how it normally behaves. A chicken will behave differently than a macaw, or an emu. There are many behaviors that are universal. All birds should be alert and observant to their surroundings. The level of interaction may vary depending on the individual’s socialization, and different species will interact in different ways. A normal bird is typically active, and stands upright on both legs, though sometimes may rest on one leg. The head is held upright, and the wings are folded and held against the body. Feathers should be smooth and flow seamlessly together over the body.

Birds disguise their pain to avoid attracting predators and to mask weakness within their flock (Mikoni et al. 2023). While species-­specific presentations of pain may vary, in general, the same symptoms can be seen across all birds. For example, a decrease in appetite can be seen in any species, yet a decrease in egg production may only be appreciated in egg production species like chicken or quail. Different types of pain such as acute or chronic, somatic or visceral, and neuropathic pain may also affect the symptoms of pain that a bird expresses and our ease in detecting it (Mikoni et  al.  2023). Changes in behavior can also be graded on severity. For example, a bird may not eat from a bowl, but still accept treats by

4.13 ExoticSpeciesPainRecognitionand Scoring

Table 4.5  A list of large animal pain assessment tools. Species

Pain assessment tool name

Tool acronym

Type of pain

Horses

Activity budgets scoring

—­

Acute (orthopedic)

—­

Activity budgets scoring

—­

Acute (colic)

Not validated

Obel Laminitis Scale

OLPI

Acute/Chronic

Not validated

Multifactorial numerical rating equine composite pain scale

ECPS

Acute orthopedic, Post-­op GIT

Validated

Modified composite pain score

MCPS

Hoof pain

Not validated

Composite measure pain scale

CMPS

Acute (LPS-­induced transient synovitis)

Not validated

Post-­abdominal surgery pain assessment scale

PASPAS

Acute (post abdominal surgery)

Initially validated

Equine Acute Abdominal Pain Scale

EAAPS

Acute (colic)

Validated

Horse Grimace Scale

HGS

Post castration, laminitis

Not validated

Equine Pain Face

EPF

Clinical pain, experimental

Validated

Equine Pain Scale

EPS

Acute/Chronic

Not validated

EQUUS-­Composite Pain Assessment

EQUUS-­ COMPASS

Acute (colic)

Validated

EQUUS Facial Assessment of Pain

EQUUS-­FAP

Acute (colic)

Validated

UNESP-­Botucatu

UNESP-­ Botucatu

Acute

Not validated

Facial action coding system

EquiFACS

Facial expressions of ridden horses

FEReq

Orthopedic

Not validated

EQUUS Facial Assessment of Pain in Foals

EQUUS-­FAP Foals

Acute

Not validated

Horse Chronic Pain Scale

HCPS

Chronic

Not validated

EQUUS-­Donkeys-­Composite Pain Assessment

EQUUS-­ DONKEY-­ COMPASS

Acute (colic and orthopedic)

Not validated

EQUUS-­Donkeys-­Facial Assessment of Pain

EQUUS-­ DONKEY-­FAP

Acute (colic and head-­related)

Not validated

Donkey Pain Scale

DOPS

Acute (post castration)

Validated

Donkeys

Validation

Not validated

(Continued)

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Table 4.5  (Continued) Species

Pain assessment tool name

Tool acronym

Type of pain

Validation

Cattle

Subjective and objective assessment of pain and discomfort

SOAPD-­VP

Lameness

Not validated

Assessment of visceral pain in dairy cattle

—­

Acute, surgical

Not validated

UNESP-­Botucatu unidimensional composite pain scale – cattle

UNESP-­ Botucatu

Acute

Validated

Cow Pain Scale

CPS

Acute/Chronic

Validated

UNESP-­Botucatu-­Pain assessment on facial expression

UNESP-­ Botucatu

Acute (male castration)

Not validated

Sheep facial expression scale

SPFES

Footrot and mastitis

Not Validated

Lamb grimace scale

LGS

Acute

Not Validated

Sheep grimace scale

SGS

Post-­operative distress and pain

Validated

UNESP-­Botucatu composite scale in sheep

USAPS

Acute postoperative abdominal pain

Validated

Numerical Rating Scale

NRS

Acute (orthopedic)

Not validated

Pain mitigation strategies in goat kids

—­

Disbudding

Not validated

Health related quality of life for farmed pigs

HRQL

Quality of life and welfare

Validated

Piglet grimace scale

PGS

Castration, tail docking

Not Validated

UNESP-­Botucatu pig composite acute pain scale

UPAPS

Acute

Validated

Sheep

Goats

Pigs

hand. A bird may have reduced activity, or worse it may sit in a corner with a dropped-­head posture. Birds in pain will be less active, and this may present with a reduction in locomotion, head movements, preening, bathing, sexual behavior, defensive behavior, or perch use. They may be less interactive with their ­owners, clinic staff, or novel objects introduced to the enclosure. In contrast, pain may lead to an increase in jumping, wing-­flapping, vocalization, and defensive and escape

behaviors. Crowns may be erected in defense of pain, as opposed to their territorial or sexual displays, while the rest of the feathers may be ruffled and ungroomed. Feather destructive behavior and self-­mutilation may occur over a painful area. Pain may produce a limp or decrease weight-­bearing on a leg. Painful birds may withdraw from handlers and have a change in temperament, either becoming suddenly aggressive or becoming amenable to handling when normally aggressive. They may hold their beak open, close

4.13 ExoticSpeciesPainRecognitionand Scoring

their eyes, or have rapid changes in pupil size. Their posture may be lowered, with their head down or tucked in.

4.13.4  Developing a Pain Score in Birds Validated pain scores in birds have yet to be developed. Studies describing the effects of specific analgesics have created pain schemes specific for their projects. After the surgical induction of lameness in pigeons, one study graded the pigeon’s attitude toward the observer, position of the fractured limb, the

amount of motor activity in a 10-­minute video recording and gave a subjective grade of pain compared to before the surgery (Desmarchelier et al. 2012). Dr. Paul-­Murphy’s group studied analgesics after experimentally inducing arthritis in Hispaniolan parrots and created a scoring ­system to assess the benefits of each drug. They graded activity, locomotion, perching, appearance, attitude, the presence of grooming behaviors, and the use of the affected limb (Paul-­Murphy et al. 2009). See Table 4.6 for an example of a pain scoring system for birds

Table 4.6  Pain scoring system for birds (nonvalidated). There are no validated pain scales in birds, yet there is a need for objective pain assessment in our avian patients. This is an example of a pain scoring system created from the common symptoms of pain observed in birds, which can be adapted for use in the veterinary clinic. Bird pain scoring Accommodate for species-­specific behaviors and the differences between wildlife, pet birds, and individual socialization levels. Stress may both present with the same symptoms as pain, or mask pain. Score

Score

Score

Score

Score

Score

Total

0

Alert, responsive and interactive with environment (toys, other birds/people, etc.)

1

Quiet, less interactive with environment

2

Depressed, inactive and unengaging

0

Normal appetite; visits food dish regularly

1

Decreased appetite; visits food dish less than normal

2

Hyporhexic/anorexic; not observed to visit food dish

0

Regular maintenance behavior (preening, wiping beak, stretching legs/wings, etc.)

1

Few maintenance behaviors

2

No maintenance behaviors observed

0

Mobile, perches, and moves both horizontally and vertically with frequency

1

Can perch, but moves slowly and occasionally

2

Avoids changing location, does not perch and remains on floor

0

No attention or change to any particular area

1

Occasional focal pecking/biting, decreased weight-­bearing on a limb, or wing held awry

2

Consistent overgrooming/biting area, non-­weight-­bearing leg, or wing dropped

0

Head and body held erect, with wings tucked and tight to body

1

Head tucked and/or wings dropped

2

Body dropped, leaning, or lying on the floor

12

Suggest additional analgesia with a score > 2, or a score of 2 in any individual section.

81

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4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species

which can be adapted for use in veterinary clinics until a validated pain score is developed. When using a pain score, acknowledge that our detection and grading of pain in birds is imperfect, and thus do not ignore clinical judgment that may not agree with the value obtained. If a condition or procedure is deemed painful in mammalian species, it is likely painful in birds as well.

4.14 ­Reptiles Reptiles and other “lower vertebrates” such as amphibians and fish have been historically part of a debate on whether they feel pain at a level of conscious perception tied to emotion, or if they simply have an adaptive reflexive response to noxious stimuli. The current common consensus is that they do perceive pain at some level. For the naysayers, one must consider the historical and ethical dilemmas by outright denying analgesia where anatomical and physiological processes still elude us, and that it is at least the more humane presumption until further evidence solidifies that they do, or do not. Broadly, reptiles do have the anatomical neural pathways that sense noxious stimuli and carry the information to the brain for interpretation (Perry and Nevarez 2018).

4.14.1  Appearance of a Nonpainful Reptile With over 11,000 species, it is hard to stereotype what normal is for all reptiles. Exceptions exist to nearly every rule of thumb with the plethora of anatomical, behavioral, and physiological adaptations found in this class of animals. Pet reptiles should appear to be aware and responsive to their surroundings with a head-­up, alert posture. For species that remain still as a means of camouflage, their facade ends when picked

up, held, and examined. When walking, many reptiles lift their bodies up and off the ground. There are many ­exceptions to this as many species employ other means of locomotion, none more obvious than the snakes and legless lizards. Changes in locomotive habits may be a presenting complaint and should not be overlooked. Most common pet reptiles tolerate handling and may only need minimal restraint. Many reptiles remain fearful of people, and aggressively defensive behavior can be normal, especially when escape routes are eliminated.

4.14.2  Appearance of a Reptile in Pain A painful reptile may be difficult to ascertain, yet they may exhibit behaviors and behavioral changes that indicate pain. Reptiles lack the facial musculature to create the expressive changes of pain that are prevalent in mammals (Benn et al. 2019). Hence, developing grimace scales is not applicable for reptiles. A painful reptile often has closed eyes and may exhibit darkening of the skin. A reduction or absence in normal behaviors such as basking, swimming, climbing, cage exploration, or a lack of interaction with conspecifics, their keepers, or clinical staff is a subtle, but noteworthy change. Reptiles may also change from passive to aggressive, or vice versa (Perry and Nevarez 2018). Hyporexia or anorexia is a common symptom of pain and often the presenting complaint by the owner. Environmental temperatures and stress may be the most common reason for anorexia in reptiles, yet when these cannot explain the symptom, pain must be considered. Changes in posture can be an indication of pain. This may be holding the head away from the body, a hunched posture, or ­guarding or rubbing an area (Perry and Nevarez  2018). During the physical exam, exaggerated flinch or withdrawal responses during palpation ­indicate pain in that region. A stiffness or

4.14 ­Reptile

avoidance in bending a joint or the spine is an indication of pain; often noticed as an intermittent or irregular kink, or avoidance to coiling in snakes. In rare circumstances, snakes have been observed to bite and then swallow their tail and caudal body. It has been theorized that this is a symptom of pain, yet published material on the matter is lacking. Reptiles do not typically vocalize in response to pain, however sulcata tortoises, Centrochelys sulcata, will often grunt and forcefully exhale when they show other clinical signs associated with large bladder stones, such as straining to urinate, blood in the urine, constipation, and cloacal prolapse. Vocalization has also been noted in Speke’s hinge-­back tortoises, Kinixys spekii but not Nile crocodiles, Crocodylus niloticus, in

nociception studies involving those species (Kanui et al. 1990; Makau et al. 2021).

4.14.3  Developing a Pain Score in Reptiles There currently is no widely accepted pain scoring scale in reptiles as seen in dogs, cats, and horses. Nonetheless, there is benefit to objectively quantifying pain in reptiles in a standardized way. At the very least, it offers a systematic approach to assure that every patient’s analgesic needs are not overlooked. See Table 4.7 for an example of a reptile pain scale made from the symptoms of pain already discussed. Consideration must always be made to allow for the flexibility surrounding the diversity of species. For example, we would not

Table 4.7  Pain scoring system for reptiles (nonvalidated). Pain can be difficult to ascertain in reptiles and there is no validated pain scale for this class of animals. It is important to objectively assess pain in reptile patients. This example of a reptile pain scale is based on the symptoms of pain observed in reptiles and can be used until a validated pain score is developed. Reptile pain scoring Ensure that the animal is in its Preferred Operating Temperature Zone (POTZ) during assessment. Accommodate species-­specific behaviors in your assessment. Score

Score

Score

Total

0

Alert, responsive, normal behaviors

1

Lack of normal behavior noticed at home/in enclosure

2

Lack of interaction to examiner, eyes may be held closed

3

Change in behavior. Aggressive animal becomes passive, or vice versa. Skin may be darker in many lizards.

0

Normal appetite

1

Reduced food intake and/or difficulty apprehending food

2

Anorexia

0

Normal posture and ambulation

1

Change in posture such as head held up and outward, or a hunched posture

2

Patient guards or rubs an area, or a limp or other lameness is present.

3

There is an exaggerated flinch/withdrawal with palpation.

8

Suggest additional analgesic measures with a score of 3 or more.

83

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4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species

want to underestimate the pain in a garter snake because it cannot close its eyes or darken its already black skin. In this example, it suggests additional analgesic measures with a score of 3 or more. Every case is different, and clinical judgment may find use of analgesics at a lower score. It must also be noted that should there be a patient that does not display symptoms of pain but has the conditions for pain (surgery, bone fracture, etc.), it should still be presumed that pain is present, and our ability to detect it is not.

4.15 ­Amphibians and Fish With over 30,000 species of fish alone and only a tiny fraction of both amphibians and fish species studied, the debate is still out on whether fish and amphibians, much like reptiles, have a conscious perception of pain, or live their lives with only adaptive behaviors to  pain. In studies trying to answer this ­question, researchers have found profound differences in response to various noxious stimuli among differing species of the same class. Behavioral changes are noted in both fish and amphibians during and after, even hours after, a painful stimulus was elicited, or  a painful procedure was performed. Interestingly, these changes in behaviors are mitigated or minimized when analgesics were used, suggesting some level of continued and awareness of pain.

for a nonpainful animal almost impossible given the thousands of different species. However, the caretaker’s assessments and notes on feeding may allude to what would be considered abnormal for that animal and should be used to assess if analgesics are appropriate.

4.15.2  Appearance of a Painful Fish and Amphibian As mentioned above, there are too many species to precisely describe what a “painful” fish or amphibian looks like, although there may be some behavioral and physiologic indicators. Changes in behavior, such as dullness or lack of environmental engagement, may be clues as to whether an animal may be in pain. Deakin et  al. (2019) developed the Fish Behavior Index (FBI) for zebrafish for fish used in research. Feeding patterns and even the animal’s body color or gill color may be affected by pain states. Fish may also have a change in their swimming patterns or hide, while arboreal amphibians may not climb or hide for longer periods of time. Aquatic amphibians, like fish, may have changes in their environmental engagement, while terrestrial amphibians may bury themselves or seek water to soak. Pain assessments in both classes are difficult, but analgesics should not be withheld based on the lack of validated assessments.

4.15.1  Appearance of a Nonpainful Fish and Amphibian

4.15.3  Developing a Pain Scoring Assessments in Fish and Amphibians

When fish and amphibians are in a home environment or fully acclimated to a new environment, they should appear alert. Some species by their inherent nature may tend to hide or explore, making writing an ­assessment

Currently there is only one accepted pain scoring tool for fish, specifically zebrafish. Zebrafish are a common research species (Ohnesorge et al. 2021). There are no validated pain scoring tools in amphibians.

4.16 ­Small Exotic Mammal

4.16 ­Small Exotic Mammals

general, common themes of pain can be seen between these species and all the species mentioned throughout the chapter. An animal’s dereliction in grooming, appetite, social behaviors, isolation behaviors, burrowing, nesting, and many more behaviors may be interrupted.

4.16.1  Appearance of Nonpainful Small Exotic Mammals With thousands of different species, it is nearly impossible, like the classes listed above, to give precise information about pain recognition in the numerous species under the mammalian class. Each species will have similar but unique presentations (Table 4.8).

4.16.3  Developing a Pain Score in Small Exotic Mammals Validated pain scores in most small exotic mammals have yet to be developed. However, there are several publications that describe certain pain-­related behaviors for individual species. Facial grimace scales provide an exciting and ever-­evolving pain assessment tool for a limited number of species. To date we have facial grimace scales for mice, rats, ferrets, rabbits, Japanese macaques, and cynomolgus macaques (see Figures 4.10 to 4.12).

4.16.2  Appearance of Painful Small Exotic Mammals Because this class is composed of smaller-­sized animals, they are typically prey species who readily disguise their pain to avoid attracting predators and to mask weakness. While species specific presentations of pain may vary, in

Table 4.8  A list of exotic species assessment tools. Species

Pain assessment tool name

Tool acronym

Type of pain

Validation

Guinea pig

Behavioral ethogram

—­

Acute postoperative pain

Validated

Ferret

Ferret grimace scale

—­

Acute

—­

Rabbits

Rabbit grimace scale

RGS

Acute

Not validated

Composite PS for assessment and quantification of pain in rabbits

CANCRS

Acute/Chronic

Initial validation

Bristol rabbit pain scale

BRPS

Acute

Not validated

Rabbit pain behavior scale

RPBH

Acute/Chronic

Validated

Rat Grimace Scale

RGS

Acute

Validated

Mouse Grimace Scale

MGS

Acute

Validated

Muscle-­Based Facial Movement Coding System for the Rhesus Macaque

Mac-­FACS

Acute

Not Validated

Cynomolgus Macaque Grimace Scale

CMGS

Acute

Initial validation

Muscle-­Based Facial Movement Coding System for the Chimpanzee

Chimp-­FACS

Acute

Not Validated

Rodents Primates

85

86

4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species

Figure 4.10  Ferret grimace scale. Source: Reijgwart et al. (2017) / PUBLIC LIBRARY OF SCIENCE (PLOS) / CC BY 4.0.

4.16 ­Small Exotic Mammal

Not present 0

Moderate 1

Severe 2

Orbital tightening

Nose bulge

Cheek bulge

Ear position

Whisker change Figure 4.11  Mouse grimace scale. Source: Langford et al. (2010) / with permission of Springer Nature.

87

88

4 Integrating Pain Recognition and Scoring in Companion, Equine, Food and Fiber Species, and Exotic/Lab Animal Species Orbital Tightening

Not Present (0) Moderately Present (1) Obviously Present (2) The eyelid is partially or completely closed. The globes themselves may also be drawn in toward the head so that they protrude less. If the eye closure reduces the visibility of the eye by more than half, it would be scored as ‘2’ or ‘obviously present’.

Cheek Flattening

Not Present (0) Moderately Present (1) Obviously Present (2) Contraction around the muzzle so that the whisker pads are pressed against the side of the face. The side contour of the face and nose is angular and the rounded appearance of the cheeks to either side of the nose is lost.

Nose Shape

Not Present (0) Moderately Present (1) Obviously Present (2) The nares (nostril slits) are drawn vertically creating a more pointed nose that resembles a ‘V’ more than a ‘U’. The tip of the nose may also be tucked under towards the chin exaggerating this appearance.

Whisker Position

Not Present (0) Moderately Present (1) Obviously Present (2) Whiskers are straightened and extended horizontally or pulled back toward the cheeks instead of the normal position where whiskers tend to have a gentle downward curve.

Ear Position

Not Present (0) Moderately Present (1) Obviously Present (2) Normally the ears are roughly perpendicular to the head, facing forward or to the side, held in an upright position away from the back and sides of the body with a more open and loosely curled shape. In pain the ears rotate away from normal position face towards the hindquarters, tend to move backward and be held closer to the back or sides of the body and have a more tightly folded or curled shape (i.e. more like a tube).

Figure 4.12  Rabbit grimace scale. Source: Keating et al. (2012) / PUBLIC LIBRARY OF SCIENCE (PLOS) / CC0 1.0.

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Mogil, J.S., Pang, D.S.J., Guanaes Silva Dutra, G., and Chambers, C.T. (2020). The development and use of facial grimace scales for pain measurement in animals. Neuroscience and Biobehavioral Reviews 116: 480–493. https:// doi.org/10.1016/j.neubiorev.2020.07.013. Monteiro, B.P., Lascelles, B.D., Murrell, J. et al. (2022). 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. Journal of Small Animal Practice 64 (4): 177–254. https://doi.org/10.1111/ jsap.13566. Morton, C.M., Reid, J., Scott, E.M. et al. (2005). Application of a scaling model to establish and validate an interval level pain scale for assessment of acute pain in dogs. American Journal of Veterinary Research 66 (12): 2154–2166. https://doi.org/10.2460/ajvr. 2005.66.2154PMID: 16379662. Monteiro, B.P. (2020). Feline Chronic Pain and Osteoarthritis. The Veterinary Clinics of North America Small Animal Practice 50 (4): 769–788. doi: 10.1016/j.cvsm.2020.02.003. Epub 2020 Apr 27. PMID: 32354489. Mücke, M., Cuhls, H., Radbruch, L. et al. (2021). Quantitative sensory testing (QST). English version. Schmerz 35 (Suppl. 3): 153–160. English. https://doi.org/10.1007/s00482-­ 015-­0093-­2 PMID: 26826097. Nawroth, C., Prentice, P.M., and McElligott, A.G. (2017). Individual personality differences in goats predict their performance in visual learning and non-­associative cognitive tasks. Behavioural Processes 134: 43–53. https://doi. org/10.1016/j.beproc.2016.08.001. O’Donnell, E.M., Press, S.A., Karriker, M.J., and Istvan, S.A. (2020). Pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs. American Journal of Veterinary Research 81 (9): 739–746. https://doi.org/10.2460/ajvr. 81.9.739PMID: 33112166. Ohnesorge, N., Heinl, C., and Lewejohann, L. (2021). Current methods to investigate nociception and pain in zebrafish. Frontiers in Neuroscience 15: 632634. https://doi.org/ 10.3389/fnins.2021.632634.

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5 Analgesia Pharmacology Darci Palmer 1,2 and Stephen Niño Cital2,3,4 1

Tuskegee University College of Veterinary Medicine, Tuskegee, AL, USA Veterinary Anesthesia Nerds, LLC, Sheridan, WY, USA 3 Howard Hughes Medical Institute at Stanford University, Stanford, CA, USA 4 Remedy Veterinary Specialists, San Francisco, CA, USA 2

5.1 ­Introduction There are numerous pharmaceutical agents available that provide some degree of analgesia. Opioids, local anesthetic agents, and nonsteroidal anti-­inflammatory drugs (NSAIDs) remain the core analgesic drug classes used in veterinary medicine. Analgesic adjunct drugs complement the primary analgesic drug classes to provide enhanced analgesia. A thorough understanding of pharmacology is required to select combinations of analgesic drugs that synergize together to provide the best pain management plan for both acute and chronic pain.

5.2 ­Definitions Absorption  describes the process of how the drug enters the blood from its site of administration (oral, IM, SC, etc.). Depending on the site and route of administration, drugs may have to cross numerous cellular membranes before reaching its target site.

Affinity  the strength of the attraction between a drug and a receptor. Allosteric binding site a binding site on a receptor that is not the primary active binding site but can partially activate the receptor. Analgesic Drug a drug that reduces or eliminates pain. Analgesic Adjunct a drug that has analgesic properties but should not be used as the sole pain-­relieving drug. Bioavailability the amount of drug administered that appears in the bloodstream after dosing. Biotransformation changing of a drug into active or inactive metabolites through a variety of chemical reactions; also known as metabolism. Concentration the amount of active drug in a given volume or mass. Also referred to as “drug strength.” Continuous Rate Infusion (CRI) administering a drug as a continuous intravenous infusion. After a loading dosage, a drug can typically be maintained at a lower dosage when administered as a CRI.

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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Box 5.1  Dosage vs. Dose Dosage and dose are often used interchangeably in literature, which can make interpretation difficult. Human medicine primarily relies on a set dose (e.g. mg) per age. Body weight is not used for most over-­ the-­counter drugs intended for human use. In veterinary medicine, it is inappropriate to rely on a set dose per patient given the large variation of size within a species or breed.

Distribution movement of a drug from systemic circulation to its intended target tissue or organ. Dose the amount of drug that is administered to the patient at one specific time point. The dose is determined by taking the weight of the patient and multiplying by the dosage. Dosage amount of medication based on units per weight of patient (e.g. mg/kg, mg/lb, ml/kg, etc.). The quoted dosage is generally determined by initial research conducted on the drug prior to release and may be based on the species or intended use of the drug. Efficacy maximum effect a drug can achieve once it reaches systemic circulation. Excretion how a drug leaves the body; also known as elimination. First-pass effect a type of drug clearance where a drug absorbed in the gastrointestinal tract travels via the portal venous system to the liver where it undergoes hepatic metabolism to an inactive metabolite and is then excreted before it even reaches systemic circulation. Drugs may have differing rates of first-­pass metabolism. Half-life the time it takes for the plasma drug concentration to fall by 50% and depends upon the volume of distribution and clearance. It is used to determine dosing frequency (interval), steady-­state plasma concentrations, and the “washout period” required for food-­producing animals.

Tissue distribution drugs not only bind to plasma proteins/receptors, but they also bind to tissue specifically and nonspecifically which contributes to the overall volume distribution of the drug. Loading dosage the dosage (e.g. mg/kg or mcg/ kg) required to achieve a therapeutic effect. Most drugs require a loading dose prior to starting a CRI so that the drug is within therapeutic range before utilizing lower dosages. Mechanism of Action (MOA) broad term to describe how a drug works within the body. Orthosteric binding site the orthosteric binding of a molecule means it is at the active binding site for the receptor that can compete with endogenous molecules. Pharmacodynamics (PD) the study of the effects of drugs, drug concentration-­effect relationships, and mechanism of action. Refers to what drugs do to the body and how they do it. Pharmacokinetics (PK) the study of how drugs move through the body. Refers to what the body does with the drug and involves absorption, distribution, biotransformation (metabolism), and excretion (ADME). All these factors will play a role in determining the concentration of the drug that reaches the target site. Potency the amount of drug required to produce its clinical effect. Therapeutic Index the ratio between the toxic dose and therapeutic dose that is used to determine the relative safety of a drug.

5.3 ­Analgesic Drugs Box 5.2  Adverse Drug Effects Always call the drug manufacturer to report an adverse reaction from a drug. Ensure the proper dosage is utilized for the intended purpose of the drug. Check for drug interactions that might occur with the concurrent use of other drugs. Many times, an adverse drug effect is due to how we are using the drug rather than the drug itself.

5.4  ­Opioid

Box 5.3  Narcotic vs. Opioid Narcotic was once commonly used to describe illicit drugs that included all opiates and opioids plus other drugs such as hallucinogens that have high abuse potential. According to the Center for Disease Control and Prevention (CDC), the term narncotic is no longer commonly used and has been replaced by the term opioid to help simplify terminology. Opioid is a broad term that encompasses natural, synthetic and semi-­synthetic drugs that relieve pain. The term opiate refers only to naturally occurring opioids such as heroin, morphine, codeine, and opium (see https://www.cdc. gov/opioids/basics/terms.html).

5.4 ­Opioids Opioids are classified by their action at the opioid receptors: pure agonists fully stimulate the opioid receptors (predominantly mu receptors); agonist/antagonists block one type of opioid receptor, while stimulating another; partial agonists bind to an opioid receptor but are less efficacious compared to pure agonist drugs; pure antagonists will attach to the opioid receptors but do not activate the receptor (reversal agents) (Pathan and Williams 2012). Synthesized opioids are a commonly used analgesic in both human and veterinary ­medicine. They mimic compounds the body produces known as endogenous opioids, more specifically endorphins, enkephalins and dynorphins. Opioids, whether endogenous or synthesized for medical use exert their ­mechanism of action by binding to the opioid receptors that are located at presynaptic and postsynaptic sites in the central nervous system (CNS) (brainstem and spinal cord) and in the peripheral tissues. Opioid receptors are part of the G-­protein coupled receptors family, which also include serotonin and endocannabinoid receptor types. Opioids work at

s­ everal locations along the pain pathway, ­mediating both ascending and descending pain pathways. They diminish transduction that occurs in the peripheral tissues, and they also dampen modulation and perception of pain that occurs in the dorsal horn of the spinal cord (central effect). They can be administered IV, IM, SQ, epidurally, intrathecal (subarachnoid, spinal), intraarticular, interpleural, orally, and rectally (James and Williams 2020). There are three commonly accepted types of opioid receptors, mu (μ), kappa (κ), and delta (δ). Other classifications commonly used in research are OP3 or MOP (mu), OP2 or KOP (kappa) and OP1 or DOP (delta). The  International Union of Pharmacology ­recommends the OP 1–­3 classification, while molecular biology nomenclature uses MOP, KOP, and DOP. Besides the three commonly accepted receptors there are opioid-­like ­receptors that have also been described, such as GPR55, ORL1, and LC123 (Mollereau et al. 1994; Bunzow et al. 1994). Advances in new opioid drugs are still underway with particular interest in synthesizing molecules with stronger affinity for the kappa and delta receptors, which may mitigate some of the adverse effects seen with opioid agonists. The kappa receptor may also be key as an anti-­ pruritic target.

5.4.1  Full Opioid Agonists This group of opioids  –­ including morphine, hydromorphone, oxymorphone, meperidine, methadone, fentanyl, remifentanil, sufentanil, alfentanil, carfentanil –­can activate all the opioid receptors at various degrees but has the greatest effect on the mu receptor due to their orthosteric binding. Because of this, they may be referred to as full mu agonists. Opioid agonists are the best option for the prevention and treatment of surgical/acute pain. They are effective at treating both visceral and somatic pain, and the effects are cumulative –­meaning that increasing the dosage or frequency of administration will provide increased analgesia.

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In dogs, opioid agonists may cause mild ­sedation due to CNS depression. Sedation is most prominent in pediatric, geriatric, or debilitated patients when opioids are used alone. Cats may show signs of excitement due to CNS stimulation when opioids are used alone or at high dosages. The co-­administration of a sedative or tranquilizer will reduce this excitement. After the administration of any opioid agonist, an initial increase in gastrointestinal (GI) motility may be seen, which can lead to defecation and flatulence. This is followed by a prolonged period of gastrointestinal stasis that may result in constipation. Opioid agonists cause miosis in dogs and mydriasis in cats. All the opioid agonists have a high risk for human substance abuse and are classified as class II-­controlled drugs by the Drug Enforcement Administration (DEA). They require a special DEA 222 form for ordering. Vomiting is a common side effect after intramuscular (IM) and subcutaneous (SC) administration. Morphine is most likely to cause vomiting followed by oxymorphone and hydromorphone. Vomiting, nausea, and anorexia are less likely to occur if the patient is already experiencing pain or if the opioid agonist is  given intravenously (IV) (Stern and Palmisano 2012). Methadone and meperidine appear to be the least likely to cause vomiting. If vomiting is contraindicated, then administer the opioid agonist after induction. A patient cannot vomit once they are unconscious. Preoperative administration of maropitant 45 minutes to 1 hour before IM administration of the opioid will help prevent vomiting. Acepromazine may also reduce the incidence of vomiting when administered before an opioid (Valverde et al. 2004). All opioid agonists will cause a dose-­ dependent decrease in respiration. However, clinically significant hypoventilation rarely occurs unless extremely high doses are

administered (Wunsch et  al.  2010). All opioid agonists (except for meperidine) will cause a dose-­dependent decrease in heart rate, blood pressure, and vasodilation. Meperidine will  likely cause tachycardia rather than bradycardia. Opioid-­induced dysphoria may occur in recovery if opioid agonists are given alone at high dosages to a patient not experiencing pain, or in patients where the dosage exceeds that which is necessary to alleviate the pain. Low dosages of sedative agents (acepromazine or dexmedetomidine) will help decrease the clinical signs of dysphoria. Partial reversal with butorphanol is also an option for the treatment of dysphoria depending on the anticipated level of pain the patient will experience in the postoperative period. Hydromorphone has been associated with causing hyperthermia in cats in the postoperative period. However, other opioids such as morphine, butorphanol, and buprenorphine have also been shown to cause postoperative hyperthermia (Posner et  al.  2010). Treatment generally consists of ice packs, fans, and placing the cat on cool metal ­surfaces. Acepromazine or micro-­dosages of dexmedetomidine may be given if the cat seems agitated and they are not contraindicated. Butorphanol can also be given as a partial reversal for other opioid agonists if the surgical procedure is not very invasive. Reversing with naloxone should only be considered in severe cases where the temperature remains elevated (> 106 ºF, 41ºC) for an extended period well beyond the duration of the drug administered. Diluting butorphanol or naloxone in sterile saline and titrating it slowly to effect (e.g. over 5 minutes) can help improve clinical signs while still maintaining analgesia. However, when using naloxone, full reversal of analgesia is always a possibility regardless of dosage utilized so other analgesics should be administered to prevent acute pain awareness.

5.4  ­Opioid

5.4.2  Individual Drug Facts Box 5.4  Efficacy vs. Potency Morphine is considered a natural opioid originating from the opium poppy plant. All synthetic and semi-­synthetic opioids used in veterinary medicine are compared to morphine regarding potency. Potency has no relation to efficacy. If a drug is more potent than morphine, it means that it takes less drug, based on dosage and concentration, to achieve its desired effect compared to morphine. It does NOT imply that the drug has more analgesic efficacy. See Table 5.1.

Table 5.1  Potency of commonly used opioids in veterinary medicine. Drug

Potency

Morphine

Original compound a

Hydromorphone

≈5×

Methadone

same as morphine

Meperidinea

0.2–0.3

Fentanylb

50–­100×

Remifentanilb

25–­50×

a

Sufentanil

500–­1000×

Alfentanilb

10–­25× c

Buprenorphine

30×

Butorphanold

4–­7×

a

 Kerr 2016  Dugdale et al. 2020 c  Bradley 1984 d  Aarnes et al. 2011 b

5.4.2.1  Morphine

Morphine has an active metabolite (morphine-­ 6-­glucuronide), which accounts for its longer duration of action compared to oxymorphone or hydromorphone. The action of this metabolite

accounts for much of the drug’s clinical efficacy. Morphine is metabolized to this active ­metabolite through glucuronidation. Cats have a decreased ability to metabolize drugs through this pathway and therefore morphine may be less ideal in cats. Morphine may cause histamine release if administered rapidly IV. Intravenous administration is best avoided in patients who present with preexisting hypotension. However, morphine used as a continuous rate infusion will not likely cause histamine release because of the low dosages that are utilized. Preservative-­free (PF) morphine is commonly used epidurally because it is less ­lipophilic than the other opioid agonists and therefore stays in the epidural space for a longer period. The duration of action of epidurally administered PF morphine has been reported to be 16–­24 hours once its effects begin ~60 minutes after instillation (Fowler et al. 2003). 5.4.2.2  Meperidine (Pethidine)

Meperidine is less potent than morphine and has a very short duration of action compared to the other opioid agonists. It will only cause mild  sedation when given alone to healthy ­animals. The short duration of action limits its use as a preoperative and postoperative analgesic. Meperidine will cause histamine release if administered rapidly IV. Meperidine is a serotonin reuptake inhibitor and should not be given concurrently with monoamine oxidase inhibitors (MAOI) or tricyclic ­antidepressants as it may induce serotonin syndrome, which is a potentially life-­threatening condition. 5.4.2.3  Methadone

In addition to being classified as a opioid agonist, methadone acts as an NMDA receptor antagonist, which is beneficial for the treatment and prevention of “windup” pain. Methadone, like meperidine, is a serotonin reuptake inhibitor and should not be given concurrently with MAOIs or tricyclic antidepressants.

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5.4.2.4  Hydromorphone

Hydromorphone may cause an intense sting reaction when administered IV. Some dogs will vocalize immediately after IV administration. The effect is transitory and tends to not require treatment. Proper restraint when administering hydromorphone IV is important to minimize injury to personnel. Panting may be observed after IM administration because it resets the body’s thermoregulatory threshold to make the body think it has an elevated body temperature. 5.4.2.5  Oxymorphone

Oxymorphone has similar effects as hydromorphone. Not commonly used in veterinary medicine as it is difficult to procure in the United States of America. 5.4.2.6  Fentanyl, Remifentanil, Sufentanil, Alfentanil, Carfentanil

Fentanyl, remifentanil, sufentanil, alfentanil, and carfentanil have a very short duration of action (15–­30 minutes), which limits their use as a preanesthetic agent. These agents are usually administered as a continuous rate infusion and used for intraoperative pain management. Fentanyl can also be used as intermittent boluses in combination with a benzodiazepine for a neurolept induction (opioid induction). Fentanyl has a context-­sensitive half-­life. When used as a CRI for greater than 2 hours, the drug will start to accumulate in the tissues. Once accumulation has occurred, the plasma concentration does not decrease rapidly once the CRI is discontinued. To prevent a prolonged recovery, it may be beneficial to decrease the fentanyl CRI rate and/or adjust the vaporizer setting about 30–­40 minutes prior to the end of surgery. The effects tend to last much longer in cats compared to dogs. Dosages of fentanyl less than 3 mcg/kg/hr will not provide sufficient analgesia for surgical/acute pain (Biello et al. 2018). Remifentanil is metabolized by nonspecific plasma esterase’s to inactive metabolites. This makes remifentanil superior to fentanyl for

patients with renal or hepatic dysfunction. It has noncumulative effects within the body, so recovery is rapid after CRI is discontinued. Alfentanil and sufentanil have a quick onset time (1–­3  minutes) and rapid elimination in dogs and cats. They are primarily metabolized in the liver and excreted by the kidneys. These agents are highly protein-­bound, so caution must be used in hypoproteinemic or hypoalbuminemic patients. Sufentanil has one of the highest binding affinities to the mu opioid receptor and may be ideal for patients who are in pain but have been previously given another competitive opioid. Carfentanil is a super opioid that is largely only used as a tranquilizing agent in megafauna such as elephants or rhinoceros. It is 10,000 times more potent than morphine and 100 times more potent than fentanyl. 5.4.2.7  Fentanyl Patches

Transdermal fentanyl patches are intended for human use but have been used regularly in dogs and cats for postoperative pain management. The patch comes in five different dosages (12, 25, 50, 75, and 100 mcg/hr), and the fentanyl is contained in a reservoir or matrix polymer. The drug is slowly absorbed through the skin over an extended period. The patch will provide up to 3–­4 days of analgesia if it is not removed for 3  days. If removed prior to 3 days, it will provide analgesia for 6–­12 hours after patch removal. The reservoir fentanyl patch has variable absorption rates in cats and is no longer commonly used (Egger et al. 2003). The matrix fentanyl patch continuously releases the drug based on the contact surface area with the skin. Fentanyl patches have a very long onset time of 6–­12 hours in cats and 12–­24 hours in dogs (Hofmeister and Egger 2004). When used, the patch should be applied while supplemental opioids and other analgesics are being administered to manage acute pain. The reservoir fentanyl patch should not be cut as that will damage the delivery membrane which could result in drug overdose (Margetts and

5.4  ­Opioid

Sawyer  2007). This is not a concern with the matrix fentanyl patch. The patch can be applied anywhere on the patient where there is intact hairless skin. The recommended application site for dogs and cats is the dorsal or lateral thorax. Where patches are placed on the animal is an important clinical decision, as it may affect the absorption of the drug depending on vascular changes due to environmental temperature changes if the patient lies on the site where the patch was placed. The absorption rate will greatly increase if the fentanyl patch comes in contact with a heat source. Toxic levels of fentanyl can be reached in a very short amount of time. Therefore, it is not recommended that a fentanyl patch be applied prior to a surgical procedure where a heat source will be used. If the skin needs to be cleaned prior to ­application of the patch most manufacturers recommend only using plain water rather than  rubbing alcohol or other detergents to clean the skin as they may affect absorption. Unfortunately, there is an increased risk of human substance abuse associated with this product. Owners should be encouraged to bring the patch back to the clinic for proper disposal. Care should be taken to prevent the patient or young children from ingesting the patch. 5.4.2.8  Codeine

Oral codeine is found in combination with acetaminophen (Tylenol® 3 or Tylenol® 4) and can be used in dogs for mild to moderate pain. This combination should not be used in cats due to the acetaminophen being toxic in this species. The oral bioavailability is only 4% in dogs but the active metabolite, codeine­6-­glucuronide, is present in high enough concentrations to provide some analgesic effects (KuKanich  2010). Oral codeine as the sole ingredient can be considered for use in cats. Unfortunately, there is only one study that assesses acetaminophen and codeine (AC) in dogs showing less efficacy in decreasing lameness scores compared to carprofen in induced synovitis. However, this study may have some

nuances in that AC is not an anti-­inflammatory, and force mats are a contentious metric in assessing pain compared to lameness alone (Budsberg et  al.  2020). All codeine products are schedule II-­controlled drugs in the USA, so human substance abuse is an issue when dispensing them to veterinary patients. 5.4.2.9  Hydrocodone and Oxycodone

Hydromorphone is the major metabolite of  hydrocodone in the dog although the ­metabolism appears to be variable among dog breeds (Benitez et al. 2015; Findlay et al. 1979; KuKanich 2013a; KuKanich and Spade 2013b). Oxycodone has been used in combination with acetaminophen but has not been studied alone as an analgesic (KuKanich  2013a; Gemba et al. 2004). Because of the generally poor oral bioavailability, as well as possible diversion to human use, these drugs are not recommended as the sole or primary analgesic in animals. Box 5.5 Oral Opioid Use in Animals The oral administration of morphine, oxycodone, hydrocodone, or methadone in dogs is not recommended. No study has been able to show analgesic effects of clinical significance. Oral bioavailability and plasma concentrations are low due to the first-­pass effect through the liver. Although no direct study has looked at oral administration of these opioids in cats it is suggested they would have the same profile as dogs because of the similarities seen with injectable opioids.

5.4.2.10  Tramadol

In the USA, tramadol is only available in tablet form and intended for oral administration. An injectable formulation is available in several other countries. Tramadol is a synthetic analog of codeine and is a racemic mixture of two enantiomers. This allows two differing affinities for various receptors and has two main mechanisms of action. It is structurally

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related to morphine and codeine and therefore has weak mu receptor agonist activity. It  also inhibits the reuptake of norepinephrine and 5-­hydroxytryptamine (serotonin) in the  CNS. Tramadol has an active metabolite (O-­desmethyltramadol; ODT or M1) that is responsible for most of the analgesic effects seen in humans (Dayer et al. 1997). This metabolite is only found in minimal concentrations in dogs after oral administration. When used alone in dogs, the clinical efficacy in providing adequate analgesia is extremely questionable and variable (Donati et al. 2021). Once a commonly used medication for acute and chronic pain, it is no longer recommended as a first-­line analgesic and should be used in combination with other, more effective analgesics such as NSAIDs (Donati et al. 2021; Guedes et al. 2018). Tramadol use is limited in cats due to the bitter taste that can make administration difficult, and it also has the tendency to cause excitement. However, it does appear to be effective and more reliable in cats compared to dogs. Tramadol should be used with caution when concurrently administered with monoamine oxidase inhibitors (MAOIs; selegiline), selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine), serotonin-­norepinephrine reuptake inhibitors (SNRIs; venlafaxine) and some tricyclic antidepressants (TCA; amitriptyline, clomipramine) as this could lead to ­serotonin syndrome. In humans with seizure disorders, tramadol is used with caution due to its potential to lower the seizure threshold. However, this effect has not been reported in animals (Beyaz et al. 2016). 5.4.2.11  Tapentadol

Oral tapentadol is a dual action mu opioid receptor agonist and norepinephrine reuptake inhibitor used in the treatment of chronic pain in humans. Although it is very similar to tramadol, it does not require metabolism to an active compound to produce an analgesic effect (Howard et al. 2018). A study assessing efficacy in dogs with unilateral lameness

concluded subjectively that the drug appeared beneficial; however, this did not correspond well to the more objective force mat. The methodology of this study could have led to better conclusions as force mat assessments alone are a contentious tool for assessing true pain relief, not only physiologically but psychologically (Kieves et al. 2020). Efficacy studies are limited in dogs and cats, but it is showing promise as a potential oral analgesic to use in small animals.

5.4.3  Partial Agonist Opioids 5.4.3.1  Buprenorphine

Historically, buprenorphine had been classified as a partial agonist at the mu receptor while having little to no effect on the kappa receptor, and thus we mention it in this section. As a partial agonist it was thought that it attaches to the mu opioid receptor but only partially activates it making it less efficacious than full opioid agonists. In addition, at dosages between 0.01–­0.03 mg/kg, it was said that buprenorphine should only be used for the treatment of mild to moderate pain. This line of thinking has been challenged and may no longer hold true (Lutfy and Cowan 2004). What is still accurate is that buprenorphine has a slower onset of action with peak effect occurring approximately 30–­45 minutes after IM injection and 15–­30 minutes after IV administration (Steagall et al. 2014). This should not be interpreted as no analgesia is provided until 15–­30 minutes after administration, rather it means the maximum effects haven’t occurred until this time period lapses. The duration of action is dependent on the dosage with a standard dosage lasting 6–­8 hours. A higher dosage will cause a longer duration of action. Buprenorphine, second to sufentanil, has the highest affinity for the mu opioid receptor which in part accounts for its long duration of action. This affinity may competitively inhibit an opioid agonist from binding to the mu receptor if administered after buprenorphine. This can pose a problem if buprenorphine is given first but then it is determined that more

5.4  ­Opioid

analgesia or a different opioid is needed later. If a full opioid agonist is administered after buprenorphine, it will likely result in longer analgesia but not necessarily added analgesia (Moreno et al. 2021). Instead, it may be more effective to give another dose of buprenorphine or rely on other analgesic drug classes if the patient appears painful. Buprenorphine may cause slight respiratory depression in animals at high dosages. In humans and animals, buprenorphine displays a “ceiling effect” on respiratory depression whereby increasing the dosage or using repeated doses will not continue to negatively impact respiratory function as may be seen with the opioid agonists (Pergolizzi et al. 2010; Dahan et  al.  2006). Buprenorphine does not produce much sedation and it is not MAC sparing at dosages between 0.01–­0.03 mg/kg and unlikely to cause vomiting (Steagall et  al.  2014). It is classified as a class III-­ controlled drug. In 2008, a shift in the understanding of buprenorphine emerged. A panel of experts in various fields convened to examine human and animal studies on the pharmacology and clinical applications of buprenorphine across species. Their goal was to establish a consensus on the interpretations of these findings. The panel concluded that in clinical settings, buprenorphine acts as a full mu agonist ­without exhibiting an analgesic ceiling effect and can be fully antagonized by naloxone (Pergolizzi et al. 2010). When interpreting agonist action in pre­ clinical studies, it’s crucial to accurately use terminology grounded in the basic principles of receptor theory, which applies mathematical principles to biological systems, enabling the quantification of drug impacts and establishing the capabilities and limitations of these systems. This approach guides the development of experiments that can subsequently refine and adjust the theoretical model. Misinterpretation or misuse of terms like intrinsic activity or efficacy, and distinctions between full or partial agonists can lead to

incorrect assumptions about a drug’s clinical effectiveness. Affinity describes the interaction between a drug and its receptor. Intrinsic activity refers to the drug’s ability to bind to the receptor and trigger a secondary response, such as G-­proteins in opioids. Efficacy goes beyond intrinsic activity, defining the magnitude of the drug’s effect or the “endpoint” within a particular system, which can vary across different tissues, species, or endpoints (like analgesia vs. respiratory depression). Therefore, terms like partial agonist should be understood as functional descriptors, context-­dependent and not inherent properties of the drug. Buprenorphine shows high affinity for the mu opioid receptor and limited intrinsic activity in laboratory assays, leading to a ceiling effect in some animal models and human respiratory depression cases (Pergolizzi et  al.  2010). Receptor theory argues against such straightforward extrapolation from one effect to another. Numerous studies have shown that buprenorphine does not act as a partial agonist at the mu opioid receptor. In animal studies, buprenorphine produces comprehensive analgesic effects. In fact, Steagall et  al. (2014) wrote, “In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported.” Moreover, human radio-­labeling studies reveal full analgesia at less than complete receptor occupancy, aligning with the definition of a full agonist. Buprenorphine also has significant anti-­hyperalgesia effects, which may offer advantages in treating neuropathic pain (Pergolizzi et al. 2010; Coe et al. 2019). Buprenorphine can be administered IV, IM, SC, oral transmucosal (OTM) or intra-­nasally (IN). Initially, OTM bioavailability in cats was thought to be as good as IV, but later research showed that sampling location skewed the results in the initial 2005 study. OTM bioavailability in cats is 20–­52% when samples are taken from the carotid artery (Steagall et  al.  2014). The OTM route should not be used if gingival

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disease is present as the absorption of buprenorphine significantly decreases (Stathopoulou et al. 2018). In dogs the OTM bioavailability is around 38–­47% when utilizing a dosage range of 0.02–­0.12 mg/kg (Ko et al. 2011). Depending on the dosage and drug concentration, OTM buprenorphine in medium and large breed dogs is discouraged due to the large volume and associated increase in cost. Numerous studies have shown that buprenorphine is less efficacious when administered SC compared to IV, IM, or OTM (Steagall et  al.  2013; Giordano et al. 2010; Steagall et al. 2020). A more recent study showed intranasal buprenorphine had a bioavailability of 57.5% in healthy male dogs when a dosage of 0.03 mg/kg was utilized (Enomoto et al. 2022). IN and OTM administration is an attractive delivery method in cats and small dogs where other analgesic formulations such as tablets or capsules make precise dosing difficult. Box 5.6  OTM vs. PO Administration of Buprenorphine Oral Transmucosal (also known as buccal) is NOT the same as administering a drug orally. The drug is administered inside the cheek pouch between the gums and the cheek and is absorbed by the mucosal membranes. Most oral drugs are swallowed, and buprenorphine and is not effective via this route due to the first pass effect through the liver.

5.4.3.2  Simbadol

Zoetis manufactures a buprenorphine product called Simbadol®. It was released to the USA market in late 2014. It is FDA approved for use in cats only. The drug has a 24-­hour duration of action if administered at a dosage of 0.24 mg/kg SC. Simbadol can be given once daily for 3 days. The concentration is 1.8 mg/ml, which is much higher than the standard buprenorphine injectable (0.3 mg/ml). A small PK study using Simbadol in dogs at 0.12 mg/kg SC failed

to show that the higher dosage and SC route responded in the same manner as cats (Hansford et al. 2021). Therefore, it is not recommended to use the box label dosage of Simbadol in dogs. Simbadol is not a sustained release product and can be used off-­label in dogs and cats at standard buprenorphine dosages (0.03–­0.05 mg/kg). Although it is approved for SC administration it can also be administered IV, IM, OTM, and IN at standard dosages. 5.4.3.3  Zorbium

Elanco manufactures a buprenorphine transdermal solution called Zorbium®. It is FDA approved in cats only. The drug is applied to the skin at the base of the neck and rapidly dries within 30 minutes after topical application. The drug forms a depot within the skin and continuously releases the drug into systemic circulation. The onset time is 1–­2 hours after application, and it will provide analgesia for up to 4 days (96 hours). The box label dosage range is 2.7–­6.7 mg/kg (~0.03–­0.07mg/kg/ hr, over 96 hours) with a concentration of 20 mg/ml and is available in two different predosed tubes. The pink tube contains 0.4 ml and should be used on cats between 1.2–­3 kg. The green tube contains 1 ml and should be used on cats greater than 3–­7.5 kg. This drug should only be administered in a hospital setting by trained veterinary personnel wearing appropriate personal protection equipment (PPE). It should not be dispensed to owners for at home use. Common adverse effects reported include two extremes where cats may experience a euphoric state of acting overly happy or they are laterally recumbent and obtunded. Anecdotally, it is recommended to use the smaller tube for all cats regardless of body weight, but this opinion has not been validated scientifically for efficacy or duration. 5.4.3.4  Sustained or Extended Release (SR or ER) Buprenorphine

Sustained release buprenorphine is available as a compounded formulation from ZooPharm

5.4  ­Opioid

for use in dogs and cats but is not an FDA approved product. The drug is administered subcutaneously and has been shown to provide analgesia for up to 72 hours. It comes in three concentrations (1, 3, and 10 mg/ml). It is known to sting on injection due to the viscous vehicle used for delivery of the drug. Several studies have been performed on this product (mostly in the UK), but none have been officially published. In the USA, sustained release buprenorphine is more commonly used in cats than dogs. Higher dosages may cause excessive sedation (especially in dogs) and may lead to a dysphoric state if the pain intensity was not as great as anticipated. Cats tend to display a euphoric state (excessive purring, rolling on floor, rubbing themselves against an object or hand, etc.). If adverse reactions occur, it can be extremely difficult to reverse this product. It may require hospitalization for supportive care and possibly a naloxone CRI. In the USA, use of SR buprenorphine is difficult to justify in small animal practice now that Simbadol and Zorbium are available. Ethiqa XR® is an FDA approved buprenorphine solution for the use in mice and rats, lasting 72 hours. This formation consists of buprenorphine suspended in a medium chain triglyceride oil at a concentration of 1.3 mg/ml. 5.4.3.5  Buprenorphine Patches

These patches are newer to veterinary medicine and appear to have good PK and efficacy studies, despite the general lack of published data and small sample sizes in the efficacy studies. The benefit of buprenorphine patches compared to fentanyl patches is the decrease in abuse by humans (Andaluz et  al.  2009; Moll et al. 2011; Galosi et al. 2022).

5.4.4  Agonist/Antagonist Opioids: Butorphanol and Nalbuphine Butorphanol and nalbuphine stimulate the kappa opioid receptor and antagonize the mu opioid receptor. They are effective at treating mild pain in dogs, cats, and exotic small

mammals. They are good at treating visceral pain but should not be used as the sole analgesic for somatic pain. Some avian species have more kappa receptors than mu, making butorphanol the opioid of choice in these select species. As sole agents these drugs only provide mild sedation in dogs and the ­sedative effects may not even be seen in cats. However, when combined with sedatives or tranquilizers, the effects of the two drugs are  synergistic and profound sedation may occur. Respiratory depression is minimal and there is little direct effect on the cardiovascular system. Vomiting is not commonly seen with these drugs. Nalbuphine is cheaper than butorphanol and has the added benefit of not being a controlled substance. Butorphanol is classified as a class IV-­controlled drug. Nalbuphine is not a controlled substance. They have a short duration of action, 30 minutes to 1.5 hours on average, and there is a ceiling effect on analgesia whereby increasing the dosage or giving repeated doses will not increase the intensity of analgesia or sedation, but it may prolong the duration of action. Butorphanol and nalbuphine can be used as  reversal agents for the opioid agonists to ­partially reverse the respiratory depression and sedation that high dosages of opioid agonists may cause while still maintaining some kappa  analgesic effect (Dalefield et al. 2022). This is called sequential analgesia.

5.4.5  Opioid Antagonists: Naloxone, Nalmefene, Naltrexone These drugs will completely reverse the adverse cardiopulmonary, sedation and analgesic effects of all the opioid drug classes. Their use should only be considered in the face of an absolute opioid overdose. In human medicine an opioid antagonist can be titrated to decrease the respiratory depression associated with opioid agonists but at the same time still maintain some beneficial analgesic effect.

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However, it is very difficult to titrate opioid antagonists in nonverbal patients without the risk of causing full reversal. Acute awareness of pain can lead  to sympathetic stimulation resulting in catecholamine release, cardiac arrhythmias, hypertension, and possible death. If titration or partial reversal is attempted with an opioid antagonist, it is obligatory that another method for providing acute analgesia is available if full reversal occurs in a painful patient. To avoid adverse effects from these agents, the total dose should be diluted in saline and titrated IV slowly to effect over 5–­10 minutes. Naloxone has an onset time of 1–­2 minutes IV and within 5  minutes IM. The duration of action is only 30–­60 minutes. Depending on the opioid being reversed, additional doses may be necessary for complete reversal otherwise re-­narcotization may occur. Nalmefene has an onset time similar to naloxone, but the duration of action is approximately twice as long (1–­2 hours). Nalmefene is approximately four times as potent as naloxone (Papich and Narayan 2021). In the USA, naltrexone is approved for opioid reversal in wildlife (e.g. deer, elk, moose) that may be darted with carfentanil or etorphine. At higher dosages in human medicine, it is used as a treatment for both opioid and  alcohol addictions. It is not commonly used for opioid reversal in dogs and cats. Interestingly, it has a variety of uses outside of its drug classification. It alters the production of interleukin-­1, tumor necrosis factor-­alpha and substance P by binding to the Toll-­like receptors (TLRs) in the CNS. This action helps to minimize chronic pain and inflammation. It also helps with the upregulation of metenkephalin found in the CNS, which may be beneficial in the treatment of immune-­ mediated disease. Use of low-­dose naltrexone has shown to be beneficial for the treatment of lick granulomas in dogs, cribbing behavior in horses, cancer patients, and chronic spinal cord injuries (Martin et  al.  2022; KuKanich et al. 2020).

5.4.6  Mixing Opioids The mixing of opioids is a highly nuanced discussion that depends on multiple factors such as dosage, time of administration, genetics, overall health status of the animal and purpose. As mentioned earlier in this section drugs like butorphanol and nalbuphine can be used as antagonist agents that will still provide some analgesia. Genetic receptor variants of opioid receptors or even the metabolism of one opioid versus another is an even more complex discussion. However, the goal of veterinary professionals should be to provide adequate analgesia in all types of situations. Depending on receptor affinity of various opioids, some may be “stickier” than others making it harder for other opioids to take its place at the receptor binding site, or competition for the same binding site especially when different opioids are given within a short period of time from one another. However, as time goes by, the opioid given first will start to naturally lose affinity, opening those binding sites for another opioid to take its place. Most opioid agonists start to lose efficacy 3–­4 hours post administration. When this occurs, it is conceivable that a second, different opioid would have some efficacy. As an example, if a low dosage (0.01 mg/ kg) of buprenorphine was given, which has a high affinity for the mu receptor, and then f­ollowed by hydromorphone, the hydromorphone would attach to the open mu opioid receptors and still provide good analgesia.

5.5 ­Non-­steroidal Anti-­inflammatory Drugs (NSAIDs) NSAIDs are primarily used for the treatment of acute, mild to moderate pain associated with any condition that produces inflammation (e.g. degenerative joint disease [DJD], dental and oral disease, surgical incision, etc.). The primary mechanism of action involves blocking prostaglandin formation via inhibition of the

5.5 ­Non-­steroidal Anti-­inflammatory Drugs (NSAIDs)

cyclooxygenase enzymes (COX-­1, COX-­2) in the arachidonic acid cascade. COX-­1 is involved with normal homeostatic functions such as renal blood flow, gastrointestinal cytoprotective mechanisms, and platelet aggregation. COX-­2 is activated by inflammatory cells and triggers the production of the inflammatory prostaglandins that contribute to peripheral sensitization and gastric ulceration. COX-­2 also serves a beneficial homeostatic role but in theory using an NSAID that selectively inhibits COX-­2  while maintaining COX-­1 activity will result in less adverse renal and gastrointestinal side effects (KuKanich et al. 2012). There are several FDA approved NSAIDs for  use in dogs: carprofen, deracoxib, etodolac, firocoxib, meloxicam, and robenacoxib (Murrell 2018). Mavacoxib is a relatively new NSAID that has a longer half-­life and duration of action compared to the others. It is not FDA approved in the USA but is used in many European Countries and Australia. All these NSAIDs have more selectivity for COX-­2  inhibition but some also have weak COX-­1  inhibition (e.g. carprofen, etodolac) (Lees et al. 2004). Carprofen, meloxicam, and robenacoxib are available in injectable and oral form while the others are strictly administered orally. In the  USA, the injectable formulation is only approved for SC administration, but in other countries some are on label to administer IV. Most NSAIDs have an onset time of 30–­60 minutes regardless of route of administration. In normal, healthy patients the administration of NSAIDs during the preanesthetic period can be very beneficial in helping combat inflammatory pain associated with surgery. However, it is common to administer the NSAID postoperative due to the concern that intra-­ operative hypotension is always a possibility even in healthy patients (Lascelles et al. 2005). Cats do not metabolize NSAIDs as efficiently as dogs because they have a deficiency in glucuronyl transferase enzymes. Caution should be taken with long term use in cats, but numerous studies have shown that short term use, or intermittent dosing (also known as pulse

therapy) can be beneficial (Monteiro et al. 2019; KuKanich et al. 2021). In the USA, meloxicam is approved for use in cats as a single one-­time dose for any given anesthetic event. In October 2010 the FDA mandated that the manufacturer of meloxicam add a boxed warning to the drug label. The boxed warning states Repeated use of meloxicam in cats has been associated with acute renal failure and death. Do not administer additional injectable or oral meloxicam to cats. Many colleagues outside of the USA have used meloxicam effectively at lower dosages and chronically. In March 2011, the FDA approved robenacoxib for use in cats in the USA. It can be administered once a day for a maximum of three days per the label, but again there is anecdote and studies to suggest long-­term use (King et al. 2021). Piroxicam is another NSAID that is used in dogs and cats, but it does not have FDA approval in the USA. Piroxicam is a nonselective COX inhibitor for both COX-­1 and COX-­2. It is primarily used in dogs and cats as an analgesic for cancer-­related pain. It is not commonly used as a standard NSAID due to the high risk of side effects. In dogs, the degree of analgesic efficacy and the development of adverse effects appear to be similar for all approved NSAIDs. Individual animals may appear to do better on one NSAID compared to another. This is most likely due to the individual response of the patient rather than the specific effects of any one NSAID. The most widely reported adverse effect of NSAID administration is gastrointestinal (GI) toxicity that may manifest as gastritis, vomiting and diarrhea, GI ulceration, or in severe cases, GI perforation. The negative effects on the gastrointestinal system are more likely to occur with inappropriate dosing or when an NSAID is concurrently administered with another NSAID or corticosteroid. If an animal has GI related signs misoprostol could be considered as a protectant (Ward et  al.  2003). NSAIDs are highly protein bound and therefore should be used with caution in patients

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with hypoalbuminemia or hypoproteinemia. Only the free or unbound drug exerts an effect on the body. If there is less protein for the drug to bind to then more drug will stay in circulation which will prolong the effects of the drug. Drug overdose can easily occur, even at standard dosages, if multiple highly protein bound drugs are given to a hypoalbuminemic or hypoproteinemic patient (KuKanich et al. 2012). NSAIDs should only be administered preoperatively if the patient is adequately hydrated. In the presence of significant dehydration, hypotension or hypovolemia, prostaglandins play a vital role in regulation of normal renal function by maintaining renal blood flow (Murrell et al. 2007). Therefore, NSAIDs are best avoided in patients that present with preexisting hypotension, hypovolemia, or renal disease. Avoid NSAIDs for any type of GI surgery that involves an incision into the stomach or bowel (e.g. gastrotomy, enterotomy for foreign body, resection, & anastomosis, etc.) (McLean and Khan  2018). Prostaglandins impact mucosal blood flow and other normal GI functions, which is important for recovery of the gastrointestinal tract after surgical insult. Long-­term use of some NSAIDs has been linked to causing hepatoxicity. However, this is a rare condition in dogs and cats (Khan and McLean  2012). Hepatopathy (increased liver enzymes) may also occur after long term use of NSAIDs. Baseline liver enzymes should be obtained before long-­term use of any NSAID is initiated and periodically measured over the course of treatment. An increase in liver enzymes may not be an indication of decreased hepatic function per se but they may be a sign that additional tests such as serum bile acids and plasma ammonia concentrations be assessed in the future (Lomas and Grauer 2015).

5.5.1  Washout In the past it has been recommended to allow at least 5–­7 days as a washout period between switching from one NSAID to another to avoid adverse effects. However, this arbitrary time

Table 5.2 NSAID types. Non-­COX selective NSAIDs

Phenylbutazone Vedaprofen Diclofenac Flunixin meglumine-­NfkB Aspirin Piroxicam Ketoprofen

COX 2 selective NSAID

Tolfenamic acid

COX 1 preferential NSAID

Ketorolac

COX 2 preferential NSAIDs

Carprofen Meloxicam

COX 2 selective NSAIDs

Robenacoxib Celecoxib Cimicoxib Deracoxib Firocoxib Etodolac Mavacoxib

Dual COX/LOX NSAID

Tepoxalin

frame has no scientific basis. Instead, the washout period should be based on the half-­ life of the individual drug in use. As a rule, 5 times half-­life results in 97% drug elimination while 10 times half-­life results in 99% drug elimination. The half-­life of common NSAIDs is; carprofen 8 hours; meloxicam 12–­36 hours; robenacoxib 1 hour; deracoxib 3 hours (Mullins et  al.  2012; Lees et  al.  2022). Table  5.2 lists ­several types of NSAIDs.

5.5.2  Piprant Class Grapiprant (Galliprant® ) received FDA approval in 2016 for use in dogs only. It is manufactured and marketed by Elanco™. It is indicated for use in dogs to control pain and inflammation associated with osteoarthritis and comes in 20, 60, and 100 mg flavored tablets for oral administration. This drug is unique in that it does not inhibit the cyclooxygenase (COX) enzyme. Instead, grapiprant is the first drug in the piprant drug class and is classified as a prostaglandin E2 (PGE2)

5.7 ­Cannabinoid

receptor antagonist (PRA). It specifically blocks the EP4 receptor, which is the primary mediator of canine osteoarthritis pain and inflammation. Because it does not have any effect on the COX enzyme, it has minimal interference with normal homeostatic functions; therefore, the side effects such as gastrointestinal disturbance are minimal.

5.6 ­Corticosteroids There is often a love–­hate relationship with corticosteroids for veterinarian professionals. Corticosteroids act as anti-­inflammatory agents by blocking prostaglandins and leukotrienes completely. They inhibit prostaglandins at the level of phospholipase A2, which results in blockage of the COX pathway similarly to NSAIDs. Corticosteroids are sometimes selected in cases as an adjunct for chronic pain management where profound anti-­inflammatory effects can be beneficial, nevertheless, they are not without potential side effects. They are also often used in neurologic conditions and even cancer related symptoms which can include pain. Long-­term corticosteroid administration can lead to panting, polyuria, polyphagia, polydipsia, behavioral changes, immunosuppression, increased risk of infection, decreased wound healing, gastrointestinal upset or ulceration, muscle and bone weakening, protein catabolism, iatrogenic Cushing’s disease, predisposition to diabetes, alopecia, chemotherapy treatment interference, and laminitis (Belshaw et  al.  2016). Corticosteroids should never be administered simultaneously with NSAIDS or other corticosteroids because of a profound risk of gastrointestinal side effects including ulceration, GI perforation, and potentially sepsis or death. However, if an animal is on a physiologic dose of steroids, one could use NSAIDs concurrently with heightened monitoring. Agents that are selected most include tablet or liquid prednisone or prednisolone (in cats). Long-­duration injectable agents (e.g. Depo-­Medrol) are used less frequently due to their sustained and irreversible effects.

5.7 ­Cannabinoids Cannabinoids are a class of compounds ­produced by the body known as endogenous cannabinoids or endocannabinoids, synthesized in a lab setting or harvested and purified from plants, mainly the cannabis plant, known as phytocannabinoids. For the purposes of this  text, we will focus on phytocannabinoids such as cannabidiol (CBD) and Delta-­9-­ tetrahydrocannabinol (THC). However, there are well over 120 different phytocannabinoids that have been discovered with each having their own unique pharmacological profile. CBD has become a popular supplement over the last several years with its primary mechanism of action on the endocannabinoid receptors, cannabinoid receptor 1 (CB1), and cannabinoid receptor 2 (CB2). However, both endogenous cannabinoids and exogenous cannabinoids (synthesized or phytocannabinoids) have been found to also have affinity for several other types of receptors including but not limited to opioid receptors, NMDA receptors, serotonin receptors, TRPV receptors and dopamine receptors. Some phytocannabinoids, primarily those in the acid form like CBDA or THCA, also have cyclooxygenase inhibiting effects similar to steroids and nonsteroidal anti-­inflammatory medications. Minimal negative side effects have been described that are specific to the cannabinoids themselves, but rather the formulations used. Common side effects include gastrointestinal upset, changes in behavior, lethargy, and inappetence. In multiple studies canines receiving a CBD product have an elevation of  alkaline phosphatase (ALP); however, newer  evidence shows this is not associated with hepatic insult (Bradley  et  al. 2022). Certain cannabinoids, like THC, can have an intoxicating effect predisposing animals to more severe complications like urinary ­incontinence and aspiration pneumonia. Pharmacokinetic data in dogs, cats, bovids, equids, rodents and birds show good absorption when ingested orally and several studies

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have been conducted for various clinical applications. More on cannabinoids can be found in Chapter 17.

intercostal, intraarticular, epidural, intrathecal (or spinal), and intravenous for regional limb perfusion (­lidocaine only) (Weil et al. 2007).

5.8 ­Local Anesthetics

5.8.1  Nocita

Local anesthetics are the most widely used drug class for neuraxial anesthesia and peripheral nerve blockade. For more on local anesthetic drugs please see Chapter 6. These are the only agents capable of completely blocking the transmission of nociceptive stimulation which prevents the signal from reaching the CNS. All local anesthetics share a common chemical structure made up of an intermediate hydrocarbon chain (ester or amide) that links together a lipophilic benzene ring (aromatic ring) and a terminal amine group. The terminal amine can either be tertiary (lipid soluble) or quaternary (water soluble). The aromatic ring determines the degree of lipid solubility while the terminal amine can exist in either lipid-­soluble or water-­soluble conformations. Local anesthetics are classified as amino-­esters (hydrolyzed by plasma cholinesterase) or amino-­amides (metabolized by the liver) (Datta et al. 2009). Amino-esters  include cocaine, chloroprocaine, procaine, proparacaine, and tetracaine. These agents are associated with a high rate of hypersensitivity reactions and are not commonly used in veterinary medicine. The one exception is proparacaine, which is used as a topical ophthalmic anesthetic agent. Amino-amides  include lidocaine, mepivacaine, bupivacaine, levobupivacaine, and ropivacaine. These agents have a low incidence of causing allergic reactions and are commonly used in veterinary medicine (Lambert 1994). Local anesthetics have a wide variety of applications and are generally selected based on their onset time and duration of action. They may be administered via various routes to include topical, subcutaneous (local  infiltration), perineural, intraperitoneal, interpleural,

Nocita® is a bupivacaine liposome injectable suspension (extended release) product. It was FDA approved for use in dogs in 2016 and cats in 2018. It provides postoperative analgesia for up to 72 hours. The drug is administered as an infiltrative block using a moving needle technique to inject the suspension into all tissue layers surrounding the surgical incision prior to closing the incision. The bupivacaine is slowly released from the individual liposomes and will diffuse locally into the surrounding tissues. It is FDA approved for use in dogs for cranial cruciate ligament repair procedures and for onychectomy procedures in cats. Although it is off-­label use, many clinicians are using it for other procedures such as amputations, mastectomies, and large mass removals, etc. It can also be used for dental blocks that are performed for major surgeries such as mandibulectomy, maxillectomy or fracture repairs of the mandible or maxilla. The drug can be diluted up to a 1:1 ratio with 0.9% sterile saline or Lactated Ringer’s solution to increase the volume to sufficiently cover the surgical site. DO NOT dilute with water or hypotonic solutions as that will interfere with the liposomal particles. Once the vial is punctured it should be drawn up into sterile syringes for single patient use. The syringes can be stored at room temperature for up to 4 hours (manufacturer guidelines).

5.8.2  Systemic Toxicity The effects of local anesthetics are additive, so all these drugs have the potential to cause systemic toxicity when used at excessively high dosages or when administered intravascularly (excluding lidocaine). If local anesthetics are used in multiple concurrent blocks (e.g. dental blocks and ring blocks), it is important to ensure that the

5.9  ­Gabapeninoid

cumulative dose for all blocks stays below the recommended maximum dosage. CNS signs of toxicity include an initial phase of restlessness, agitation, ataxia, nystagmus, and muscle twitching. As plasma concentrations increase, seizures, CNS depression, unconsciousness and respiratory arrest may result. Cardiovascular signs include decreased cardiac output, vasodilation, and profound hypotension. Bupivacaine is cardio-­toxic and should NEVER be given IV. Mepivacaine should also NOT be administered IV due to the high potential for adverse neurological and cardiovascular system reactions. Ropivacaine has less chance of causing adverse CNS and cardiovascular effects when compared to bupivacaine and mepivacaine. Cats tend to be more sensitive to the effects of lidocaine and are prone to seizure activity. While local anesthetics can be used in cats, lower dosages should be utilized. Intravenous lipid emulsion has been shown to successfully treat systemic toxicosis caused by local anesthetics.

5.8.3 Lidocaine as a CRI Lidocaine is the only local anesthetic that can be administered IV. In addition to being used for intravenous regional anesthesia (IVRA), it can be used as a CRI to provide analgesia (low dosages) and as a class IB antiarrhythmic for the treatment of ventricular tachycardia (high dosages). It has MAC sparing effects, which complements the overall balanced anesthesia drug protocol (Ortega and Cruz  2011). Although the exact mechanism for providing analgesia is not well understood it is believed that lidocaine has several properties that can contribute to a decrease in intraoperative nociception. Lidocaine displays free radial scavenging effects, which may be helpful in preventing reperfusion injury; it acts as an inflammatory modulator by decreasing neutrophil chemotaxis and platelet aggregation and is a prokinetic that enhances gut motility and helps prevent ileus. Higher CRI dosages may not be  suitable in cats due to the potential for ­systemic toxicity.

5.9 ­Gabapeninoids Gabapeninoids are derived from the inhibitory neurotransmitter gamma-­Aminobutyric acid (GABA). Both gabapentin and pregabalin were readily adopted in leu of tramadol when studies showing tramadol’s failures in pain management for dogs. Unfortunately, gabapentin is not a good choice of drug for acute pain alone. For acute pain it should always be paired with at least one other proven analgesic.

5.9.1  Gabapentin Gabapentin is an amino acid molecule that binds to alpha-­2 delta on voltage-­gated calcium channels within the dorsal horn of the CNS to reduce calcium currents, preventing glutamate release in the nociceptive pathways. This is believed to be the main ­mechanism of action although other studies described ­inhibitory effects on substance P  release in afferent neurons in rats when administered spinally and intraperitoneally (Davis et al. 2020; Davari et al. 2020; Wiffen et al. 2017). Gabapentin is typically used as an adjunctive agent, meaning it is given long-­ term in conjunction with other chronic ­analgesic drugs such as NSAIDs, NMDA antagonists, and opioids. The drug is generally well tolerated in dogs and cats with transient sedation being the main clinical side effect. In canines treated with gabapentin for chronic pain, there was an improvement in quality of life. Unfortunately, in cats, there was a deterioration of quality of life yet an increase in perceived comfort was documented by the owners (Siao et al. 2010). Current dosage recommendations for ­gabapentin as an adjunct analgesic is 3–­20 mg/kg PO in canines and felines with as high as 50 mg/kg being documented. These oral dosing regimens are currently recommended for 12 hours yet gabapentin administration every 6–­8 hours may be needed to provide adequate concentrations for analgesia (Grubb 2018).

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5.9.2  Pregabalin Pregabalin is a more potent successor to gabapentin that has also been investigated for its use in chronic pain states in both people and animals. Studies have shown a successful reduction in clinical signs of central neuropathic in dogs ailed by syringomyelia. The mechanism of action mimics that of gabapentin but appears more potent and has a longer half-­life (Papich  2021). Due to the cost burden and ­controlled substance classification, it is less widely used than the inexpensive gabapentin. According to Papich 2021, pregabalin is recommended to be dosed at 2–­5 mg/kg per os (PO) every 8–­12 hours in canines. Supportive ­studies documented a dose of 4 mg/kg PO every 12 hours as appropriate in healthy dogs (Salazar et al. 2009). For treating felines, a dosage at 4 mg/kg PO provides plasma concentrations above the levels effective for 12 hours with a half-­life of 10 hours (Papich 2021). More studies are needed to further understand the side effects, proper dosing regimens and long-­ term use for our companion animals.

5.10 ­Alpha-­2 Agonists 5.10.1  Xylazine, Medetomidine, Dexmedetomidine, Romifidine, Detomidine Currently in the USA, dexmedetomidine is the commonly used alpha-­2 agonist in small animal anesthesia. It is FDA approved for use in both dogs and cats. Medetomidine is a racemic mixture of two isomers: dexmedetomidine and levomedetomidine. Dexmedetomidine is the active, more effective isomer of medetomidine while levomedetomidine was not responsible for any clinical effects. Xylazine, romifidine, and detomidine are commonly used in large animal anesthesia. The main effect of this drug class is profound sedation and muscle relaxation. These drugs also provide analgesia, but the analgesic effects are shorter duration than the sedative effects. The alpha-­2 to alpha-­1

receptor binding ratio helps determine the degree of analgesia. Xylazine has a low binding ratio of 160:1 whereas dexmedetomidine has a binding ratio of 1620:1. Therefore, dexmedetomidine provides better analgesia than xylazine. There is minimal effect on the respiratory system. Respiratory rate and minute volume may be slightly decreased but little change is seen in PaCO2. Alpha-­2 agonists can be combined with opioids for deep sedation or premedication prior to general anesthesia. They can cause up to an 80% reduction in the induction agent and a 50% reduction in the inhalant concentration (MAC sparing). Micro-­dosages of alpha-­2 ­agonists may be beneficial intra-­operatively to provide additional analgesia and sedation while keeping the inhalant concentration low. Postoperatively, a micro dosage (0.5–­2 mcg/kg IV) of dexmedetomidine can be used in conjunction with opioids to treat a rough recovery. They can also be used as a CRI in the post-­op period to help enhance analgesia and sedation while keeping the dosage of opioids at a minimum. There is a biphasic effect on blood pressure. Initially, activation of the peripheral post-­ synaptic alpha-­2 receptors results in vasoconstriction and a period of hypertension but once the central and peripheral presynaptic alpha-­2 receptors are activated it results in a sustained decrease in blood pressure due to vasodilation (blocking norepinephrine). Significant bradycardia (HR decreases by 50% of normal resting rate) is the result of two mechanisms: (i) a decrease in sympathetic drive allows vagal tone to predominate and (ii) the baroreceptor reflex responds to the initial hypertension with a reflex bradycardia. Heart rate is a major determinant of cardiac output and therefore a decrease in cardiac output also results. Bradyarrhythmias such as pronounced sinus arrhythmia, ventricular escape beats, and atrioventricular block (first and second degree) are common. Despite the intense vasoconstriction, bradycardia, and reduction in cardiac output, studies have shown that perfusion to

5.10 ­Alpha-­2 Agonist

the vital organs is maintained within acceptable range (Lawrence et al. 1996). Alpha-­2 agonists will inhibit antidiuretic hormone (ADH) and insulin release, which will cause diuresis and transitory hyperglycemia, respectively. Heavily sedated dogs may respond aggressively to touch or any stimulation after the sedation has taken effect. All sedated patients should be approached slowly and cautiously to prevent a startled bite response. Increasing the dosage of an alpha-­2 agonist will produce a state of deep sleep or hypnosis, but it will not induce unconsciousness. Alpha-­2 agonists should be avoided in patients with cardiovascular disease (e.g. grade III or above heart murmurs, heart failure, dilated cardiomyopathy, etc.). However, a study published in JAVMA suggests medetomidine may be suitable for use in cats that present with left ventricular hypertrophy and exhibit left ventricular outflow tract (LVOT) obstruction (Lamont et al. 2002). These drugs are not recommended in patients with uncontrolled diabetes because they may worsen the hyperglycemia. They should also not be used when serial blood glucose levels need to be obtained because these agents can interfere with the results (Bouillon et al. 2019). Atipamezole is the reversal agent for medetomidine and dexmedetomidine and is only labeled for IM administration. It is 10 times more concentrated than dexmedetomidine and 5 times as concentrated as medetomidine. The dosage of atipamezole is based on an agonist to antagonist ratio of 1:10. Since the concentration of atipamezole (5 mg/ml) is 10 times that of dexmedetomidine (500 mcg/ml, 0.5 mg/ ml) an equal volume of each drug can be used for easy dosing. This same dosing for atipamezole does not hold true for the 100 mcg/ml (0.1 mg/ml) dexmedetomidine. Cats can display hypersalivation and CNS excitement after reversal with a full dosage of atipamezole. Zoetis™ recommends that a half dose of atipamezole be used in this species. Yohimbine and Tolazoline are the reversal agents for xylazine. They competitively bind to

the alpha-­2 receptors and antagonize both the sedative and analgesic effects of xylazine. Tolazoline also has an effect on alpha-­1 receptors. It will cause peripheral vasodilation that will decrease peripheral vascular resistance and increase venous capacitance. The onset of action is 1–­3 minutes for yohimbine and within 5  minutes for tolazoline. Both drugs have a short duration of action and are administered IV. Dilute the total dose in 5 ml of saline and titrate slowly to effect to prevent unwanted side effects such as rapid arousal, excitement, rage, muscle tremors, salivation and/or diarrhea. These drugs may cause vasodilation, hypotension, and tachycardia if overdosed or given too fast. Their short duration of action may require repeat dosing.

5.10.2  Zenalpha® (Medetomidine and Vatinoxan) Dechra released Zenalpha in 2022 and it is FDA approved for use in dogs. It is the combination of medetomidine and vatinoxan. Vatinoxan, previously known as MK 0467, is an alpha-­2 antagonist that only acts on the peripheral post-­synaptic alpha-­2 receptors. It does not cross the blood-­brain barrier, so it has no effect on the CNS. Research has shown that the beneficial effects of the alpha-­2 agonists (e.g. sedation, analgesia) occur due to stimulation of the alpha-­2 agonists located in the CNS (brain, ­spinal cord) while the cardiovascular effects (vasoconstriction, bradycardia) occur due to stimulation of alpha-­2 receptors in the periphery (Rolfe et al. 2012). The co-­administration of vatinoxan with medetomidine preserves the central effects of the agonist while preventing or blunting the peripheral effects. Zenalpha will produce sedation and analgesia but does not cause a significant decrease in heart rate. It can be administered IM (on-­label) or IV (off-­ label) and is recommended for use in short procedures (e.g. nail trim, ear cleaning, etc.). It takes effect within 5–­10 minutes and lasts approximately 30–­45 minutes. It should not be used in cats as severe hypotension may result.

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5.11 ­N-­Methyl-­D-­Aspartate (NMDA) Antagonists 5.11.1 Ketamine and Tiletamine The dissociative agents include ketamine and tiletamine. These drugs are classified as arylcyclohexylamines and are chemically related to phencyclidine. They are both class III-­ controlled drugs. Ketamine comes as an aqueous solution (5% or 10%) with the preservative ­benzethonium chloride. The most common formulation contains a racemic mixture of two isomers: positive S and negative R. The positive S isomer has greater potency, better analgesic properties, rapid metabolism, and produces less emergence delirium than the negative R isomer (Strigo et al. 2005). Ketamine has numerous metabolites with the major active metabolite being norketamine. Norketamine acts as an NDMA antagonist exerting its effects for approximately 5 hours after administration. Tiletamine is only found in combination with the benzodiazepine, zolazepam. In veterinary medicine this drug combination is sold under the trade names, Telazol®, Zoletil®, and Tzed®. It comes as a powder and must be reconstituted with 5 ml of diluent. If sterile saline is the diluent, then the concentration is 100 mg/ ml (50 mg/ml tiletamine, 50 mg/ml ­zolazepam). Interestingly, each brand of ­tiletamine/zolazepam has different shelf-­life dates after reconstitution: Telazol –­ 7 days (room temp) or 56 days (refrigerated); Zoletil  –­ 4 days (room temp) or 14 days (refrigerated); Tzed  –­ 8 days (room temp) or 63 days (refrigerated). Both ketamine and tiletamine act as antagonists at the phencyclidine binding site on the NMDA receptor. Their action prevents glutamate and glycine from binding to the NMDA receptor, which results in depression of the thalamocortical, limbic and reticular activating systems of the brain. Dissociative agents have also been reported to act at the opioid receptors, monoaminergic receptors, and muscarinic receptors. Unlike the other injectable anesthetic

agents, the dissociative agents ­display anti-­ nociceptive properties. Analgesia is partially mediated through weak activation of the mu opioid receptors and activation of the monoaminergic receptors may also play a role in anti-­ nociception. The primary means of providing analgesia is due to blockade of the NMDA receptor. NMDA receptor activation in the dorsal horn of the spinal cord plays a pivotal role in the development of central sensitization (Ahern et al. 2013). At sub-­anesthetic dosages, ketamine and potentially tiletamine block this activation and therefore play a role in the prevention of central sensitization. Tiletamine is not well studied for its analgesic properties because of the difficulty to obtain the drug outside of the tiletamine/zolazepam combinations. Ketamine and tiletamine/zolazepam are ­primarily used as induction agents prior to inhalant anesthesia. These drugs can be administered intravenous (IV) or IM for induction. At induction dosages (3–­5 mg/kg IV; 5–­10 mg/kg IM), these agents will produce unconsciousness. With adequate sedation and analgesia, ketamine can be given as repeated IV boluses to maintain anesthesia for short procedures. At sub-­anesthetic dosages (0.3–­1 mg/kg IV) ketamine provides analgesia by blocking the NMDA receptor, but typically the clinical signs of dissociative anesthesia (e.g. muscle rigidity, salivation, central eye, etc.) are not present. Ketamine does not provide any intrinsic analgesia and therefore should not be used as the sole analgesic agent, but when administered at ­sub-­anesthetic dosages it complements other analgesic agents (e.g. opioids) and therefore contributes to the overall multimodal pain management protocol. At sub-­anesthetic ­dosages, the NMDA antagonism may allow ketamine to possess neuroprotective properties (e.g. reduces or prevents excitotoxicity). Therefore, when used with controlled ventilation, it may be beneficial in patients that present with traumatic brain injuries (Bell 2017). Ketamine is versatile in how it can be incorporated into a multimodal pain management

5.12  ­Neurokinin-­1 Inhibitor

protocol. It can be administered as a CRI after a loading dose. The loading dose can come from using ketamine as the main induction agent in combination with a muscle relaxant, as a co-­ induction agent in combination with propofol or alfaxalone or administered as a single bolus prior to starting the CRI. Recently, SC administration has gained attention as it appears that a single SC sub-­anesthetic dosage of ketamine can help with chronic pain management and have an effect up to 30 days after a single injection. More research is needed on this route and use in this manner, but anecdotal reports are encouraging. In humans, ketamine has gained popularity as a treatment option for refractory depression that is unresponsive to other treatment options (e.g. SSRI) (Kowalczyk et al. 2021).

5.11.2  Precautions/Contraindications When used at induction dosages greater than 5mg/kg, adverse effects include hypersalivation, negative inotropic effects, increased bronchial secretions and the potential for emergence delirium if the dissociative drug is the only agent on board at the time of recovery. The dissociative drugs should be used with extreme caution in patients with depleted catecholamine stores, such as in patients with shock, severe trauma, or stress. The direct depressant effects on the cardiovascular system will predominate when there are no catecholamines to stimulate the sympathetic nervous system. In cats, ketamine is not metabolized to inactive compounds before elimination in the urine. While ketamine does not have a direct toxic effect on the kidneys, the clinical effects will be greatly prolonged in patients with urinary obstruction or renal disease.

5.11.3 Amantadine and Memantine Amantadine is an NMDA antagonist (like ketamine) and can be used as an analgesic adjunct for both acute and chronic pain in dogs and cats (Moore 2016). It effectively blocks central

sensitization in the dorsal horn of the spinal cord but should not be used as a sole analgesic. Amantadine is used in human medicine as an anti-­viral medication, and it has also been used in the treatment of Parkinson’s disease. It is available in capsule and liquid form and intended for oral administration. It is excreted unchanged in the urine so it should be used with caution in patients with renal disease. Memantine is like amantadine but lacks PK and efficacy studies in animals.

5.12 Neurokinin-1 Inhibitors Neurokinin-­1 (NK-­1) antagonists, such a maropitant, selectively block NK-­1 receptors (a type of tachykinin receptor) and the subsequent ­activation of substance P. Substance P is a neurotransmitter and neuromodulator that is important in the process of pain perception as well as in the vomiting reflex. Maropitant is widely used as an antiemetic for dogs and cats to manage emesis associated with pancreatitis, gastritis, parvoviral enteritis, and chemotherapy-­ induced nausea. Literature notes with NK-­1 receptors being present in different areas of the pain pathway, both the CNS and peripheral ­tissues, that there is a possibility it would aid in the management of visceral pain, inflammatory responses, stress, and anxiety (Sharun et al. 2021). Oral and injectable formulations are available SC or IV dosing at 1 mg/kg every 24 hours and 2 mg/kg for PO administration every 24 hours. Long-­term therapy with maropitant has yet to be established beyond 14 days and more research is needed to completely comprehend the role it plays as an analgesic. While not commonly treated, maropitant has been shown to provide aid in the treatment of “chest pain” secondary to chronic bronchitis in canines and working as an adjunct for maintaining comfort levels in patients receiving cancer and/or hospice care. At this point in time, the authors are cautious not to recommend maropitant for other types of pain (Kinobe and Miyake 2020).

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5.13 ­Bisphosphonates Bisphosphonates (BP) are a class of drugs that prevent the loss of bone mass by blocking ­osteoclasts (the bone cells responsible for the breakdown of bone), thus stabilizing bone destruction and potentially helping to manage pain. In humans, BPs have supported patients with postmenopausal osteoporosis, osteogenesis imperfecta, multiple myeloma, metastatic breast as well as prostatic cancer. Similarly, bisphosphonates have been used in companion animals for alleviating bone pain associated with bone-­destructing diseases (predominantly osteosarcoma in dogs and navicular disease in horses) and treating hypercalcemia in several other species. Regrettably, these analgesic agents are not without consequences. In humans, there have been occurrences of atypical femur fractures and osteonecrosis of the jaw with long-­term therapy. Likewise, these adverse events are also reflected in our veterinary patients after prolonged usage. For instance, in felines, there are reports of jaw osteonecrosis as well as bilateral patella fractures and oral mucosal ulcerations along with mandibular bone exposure in canines (Suva et al. 2021). At this time, these drug remains an adjunctive option for additional analgesia and is often administered as follows: pamidronate 1–­2 mg/kg diluted in 250 ml 0.9% NaCl and administered IV over 2 hours. This is combined with standardized palliative radiation therapy, an NSAID, and doxorubicin or as a single agent with an NSAID. Before considering BPs for the treatment of chronic pain in any patient, a veterinary oncologist should be consulted to discuss the risk versus benefits of this potential treatment. Further studies are needed to appreciate BP efficacy in the setting of chronic pain. Pamidronate has been studied the most in animals with overall poor analgesic effects alone but a positive effect when used as an additive in combination with conventional analgesics (Fan et al. 2005, 2007, 2009).

5.14 ­Acetaminophen (Paracetamol) Acetaminophen is a centrally acting analgesic and antipyretic. Although the exact mechanism of action of these drugs is not currently elucidated, it is believed to involve the inhibition of cyclooxygenase (COX) isoform COX-­3, a splice variant of COX-­1, and via activation of the descending serotonergic pathways to produce analgesia centrally (Candido et al. 2017; Bello and Dye 2023). It is often discussed with NSAIDs, but this drug should not be classified as an NSAID because of its weak anti-­ inflammatory properties. At the appropriate dosage, analgesia results from activation of descending inhibitory serotonergic pathways and activation of cannabinoid receptors. In the USA, it is commonly found in oral formulation and is often combined with codeine for pain management in animals. The injectable formulation is now available in the USA. In the UK and other countries, injectable paracetamol is administered IV. In canines, acetaminophen has been used at 5–­15 mg/kg every 8–­12 hours PO often combined in a fixed-­dose product such as ­hydrocodone dosed at 0.22–­0.5 mg/kg PO every 8 hours (not to exceed 15 mg/kg PO every 8 hours acetaminophen) or codeine 1–­2 mg/kg PO every 6–­8 hours (not to exceed 15 mg/kg PO  every 8 hours acetaminophen) (KuKanich et  al.  2012). Anecdotally, acetaminophen seems most useful in dogs, either for short-­ term use following surgery (acute pain), during the “washout period” when changing from one NSAID to another, or for short-­term pulse therapy in chronic pain states. In most dogs, acetaminophen is well tolerated, although toxicity resulting in methemoglobinemia has been documented. Clients should give the medication exactly as directed by their veterinarian. Acetaminophen can be used with NSAIDs. It should not be used in dogs with hepatic disease. There is no data to support

5.17 ­Dipyrone (Metamizole

long-­term use in dogs, although it is commonly used chronically. Acetaminophen-­containing products should never be administered to cats since they are relatively deficient in the enzyme glucuronyl transferase, which conjugates acetaminophen to glucuronic acid for excretion. This results in a manifestation of toxicosis with severe methemoglobinemia leading to hemolysis and death.

5.15 ­Frunevetmab (Solensia®) and Bedinvetmab (Librela®) The urgency in more effective treatment options for pain related to degenerative joint disease (DJD) has led to new targets being identified. Initially, nerve growth factor (NGF) was identified for its role in the growth and upkeep of sensory and sympathetic neurons during the development of the nervous ­system. However, in mature organisms, NGF primarily acts to amplify pain sensations. Research over the years has highlighted NGF’s significance in chronic pain conditions in rodent studies and human cases, including DJD-­ related pain. Following injury or harmful stimuli, NGF levels rise. It mainly functions by binding to the tropomyosin receptor kinase A (TrkA), leading to heightened pain sensitivity and modifications in neuron characteristics (Enomoto et  al.  2019). Such alterations can result in an uptick in pain-­related neurotransmitters like substance P and calcitonin gene-­ related peptide. These are expelled from their originating terminals, initiating neurogenic inflammation. Furthermore, when NGF binds to TrkA on inflammatory cells, it can release other inflammatory agents, including histamine, serotonin, and more NGF. Therefore, NGF can initiate increased peripheral pain sensitivity and play a role in various inflammatory processes. Anti-­ NGF monoclonal antibodies (mAbs) offer a new modality for pain relief, hindering the

processes described above. Recent human trials, and now canine and feline studies, have shown that these mAbs can effectively treat moderate to severe pain in osteoarthritis-­ affected joints, with results sometimes surpassing those of traditional pain relievers like NSAIDs or opioids. In the USA, Frunevetmab (Solensia®) is FDA approved for cats while Bedinvetmab (Librela®) is FDA approved for dogs. Both the canine and feline products are administered as a SC injection once a month (Zoetis 2024).

5.16 ­Polysulfated Glycosaminoglycans (PSGAGs) Adequan® is a popular PSGAG used in the ­treatment of osteoarthritis in dogs. The exact mechanism of action is unknown, but it is thought to inhibit degradation of cartilage at the affected joint and decreases the release of inflammatory mediators. This helps to reduce pain and inflammation. Adequan® is FDA approved in dogs for IM injection twice a week for 4  weeks, although many practitioners use increased off label dosing. It is FDA approved in horses for IM injection every 4 days for a 28-­day period resulting in a total of 7 injections. This drug should not be considered as a first line analgesic but one that compliments chronic pain management strategies (McIlwraith 2016).

5.17 ­Dipyrone (Metamizole) Dipyrone, also known as metamizole, is a pyrazolone derivate. It has analgesic, antipyretic, and antispasmodic properties. It also has been shown to have action at COX-­1 and COX-­2, but it is not classified as an NSAID. It comes in oral and injectable formulations and is currently available in the USA only for horses. A recent study compared the analgesic effects of dipyrone to meloxicam in cats

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(Pereira et al. 2021). The results showed that it was as effective as meloxicam for the treatment of post-­operative pain associated with ovariohysterectomy. The oral formulation may cause excessive salivation. Many countries have banned dipyrone due to its risk of causing agranulocytosis.

5.18 ­Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs) Numerous drugs that were initially developed for people as antidepressants have become effective tools for the management of chronic pain in animals. For chronic pain, this class of drug appears to be most effective for conditions that are neuropathic in nature secondary to myofascial pain, diabetic neuropathies, fibromyalgia, and postherpetic neuralgia. These drugs predominantly work by their action on five different neurotransmitter pathways to block serotonin and norepinephrine reuptake. They also are competitive antagonists on ­postsynaptic alpha cholinergic, muscarinic, and histaminergic receptors (Moraczewski et  al.  2022). These neurotransmitters are believed to play a role in the modulation of pain within the CNS and may additionally have anti-­ inflammatory effects on microglia (Obuchowicz et al. 2006). Because chronic pain states can be psychologically and emotionally draining these agents have the potential added benefit of improving mood, reducing depression, and reducing anxiety in companion animals with chronic pain. Amitriptyline, a widely prescribed TCA, acts to reduce serotonin and norepinephrine reuptake post-­synaptically, and therefore results in  higher neurotransmitter levels. It is likely that amitriptyline also exerts analgesic effects through numerous other mechanisms including sodium, calcium, and potassium channels,

neurotrophic tyrosine kinase receptors, and potentially NMDA receptors. Potential adverse effects include altered thyroid levels, sedation, constipation, hyperexcitability, dysrhythmias, bone marrow suppression, hyperglycemia, hyponatremia, and vomiting. Caution should be used when administering concomitantly with other pharmaceuticals that would worsen the risk of adverse effects. Amitriptyline is typically dosed at 1–­2 mg/kg PO every 12 hours with some documentation of up to 3–­4 mg/kg in canines (Norkus et al. 2015). In cats for neuropathic pain, the dosing regimen is 0.5–­2 mg/kg PO every 24 hours (Jordan and Ray 2012). Patients should be monitored with bloodwork, urinalysis, and ECGs pre, intra, and post therapy. Duloxetine is a serotonin–­norepinephrine reuptake inhibitor (SNRI) that is effective for depression and anxiety disorders in humans. In people, the drug has shown benefits in treating chronic pain states such as diabetic peripheral neuropathy, fibromyalgia, interstitial cystitis, musculoskeletal pain, anxiety, cognitive impairment, and likely several more. Currently, the use of duloxetine in companion animals is minimal. Veterinary personnel should be advised that when using psychotropic agents concurrently with other drugs, drug interactions can increase serotonin to debilitating levels, resulting in a condition known as serotonin syndrome. In dogs, serotonin syndrome can cause agitation, dysphoria, vocalization, hyperactivity, muscle tremors, vomiting and diarrhea, tachycardia, hyperesthesia, panting, hyperthermia, seizures, and potentially death in severe cases. Data reflecting the exact incidence of occurrence is lacking; however, it is expected to be less than that experienced in people. Regardless, it is best to avoid mixing TCAs, SSRIs, tramadol, and SNRIs together and avoid administering them with other drugs that may also increase serotonin (e.g. MAOI like selegiline, meperidine, methadone, etc.) unless the patient is carefully monitored for adverse effects.

 ­Reference

5.19 ­Acepromazine Acepromazine is not an analgesic but can complement analgesic plans with sedation and potentially anxiolytic effects. There is a lot of contention about this drug having true anxiolytic effects. Part of the contention is that anxiety in our patients is difficult to define  –­ like pain. Anxiety is a complex emotional state that is nearly impossible to objectively quantify in nonverbal patients. Therefore, we must rely on behaviors and biochemical indices to infer what our patients might be feeling whether they are content or distressed. Acepromazine may not be the best anxiolytic for all patients and all indications. The best evidence we have supports its efficacy for acute anxiety. It is an appropriate treatment for anxiety in the hospital setting in select patients, at modern dosages (0.01–­0.05 mg/kg) (López-­ Olvera et al. 2007; Light et al. 1993). To an extent, since anxiety is a state of forebrain hyperexcitability, sedation inherently reduces anxiety. Acepromazine also shares a  mechanism of action with other drugs that have proven, dose-­dependent, anxiolytic efficacy in humans. Multiple studies across species ­consistently show that acepromazine reduces anxiety-­related behaviors and biochemical markers of stress –­except for one. Acepromazine does not directly suppress motor function, nor is it dissociative. Though the argument has been made that acepromazine “paralyzes” patients without relieving their anxiety, this claim is

inconsistent with its mechanism of action. In some veterinary patients, high-­dose acepromazine (more commonly used in the past) can cause paradoxical excitation. However, this paradoxical effect is extremely uncommon with modern dosages (López-­Olvera et  al.  2007; Light et al. 1993; de la Mora et al. 2010; Montané et al. 2003; Vaisanen et al. 2002; Costa et al. 2023; Casas-­Díaz et al. 2010).

5.20 ­Trazodone Trazodone is classified as a serotonin antagonist (5-­HT2A and 5-­HT2C) and reuptake inhibitor (SARI). It is also a histamine (H1) antagonist and alpha-­1 adrenergic antagonist. Trazodone is not an analgesic. It can be used in both dogs and cats, but it appears to be much more effective in dogs. Trazodone causes sedation and anxiolysis and is primarily used as a behavior-­ modifying drug to address anxiety related to noise phobias, separation, hospital visits, travel, and similar issues. From an anesthesia standpoint, it can also be used to help with postoperative confinement after surgery both in the hospital and home setting. It comes in tablet form (50, 100, 150, 300 mg) and is intended for oral administration only. Extreme caution should be used when combining trazodone with SSRIs, TCAs and/or MAOIs, as serotonin syndrome may result. Onset of action tends to be 1–­2 hours in dogs, but results may vary between patients.

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non-­steroidal anti-­inflammatory drugs in cats with chronic kidney disease: from controversy to optimism. The Journal of Small Animal Practice 60 (8): 459–­462. Moore, S.A. (2016). Managing neuropathic pain in dogs. Frontiers in Veterinary Science 3: 12. https://doi.org/10.3389/fvets.2016.00012. de la Mora, M.P., Gallegos-­Cari, A., Arizmendi-­ García, Y. et al. (2010). Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: structural and functional analysis. Progress in Neurobiology 90 (2): 198–­216. https://doi.org/10.1016/ j.pneurobio.2009.10.010. Moraczewski, J.A., Awosika, O., and Aedma, K.K. (2022). Tricyclic Antidepressants. National Library of Medicine. StatPearls Publishing. Moreno, K.L., Scallan, E.M., Monteiro, B.P. et al. (2021). The thermal antinociceptive effects of a high-­ concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats. Veterinary Anaesthesia and Analgesia 48 (4): 570–­576. https://doi.org/ 10.1016/j.vaa.2021.03.008. Mullins, K.B., Thomason, J., Lunsford, K.V. et al. (2012). Effects of carprofen, meloxicam and deracoxib on platelet function in dogs. Veterinary Anaesthesia and Analgesia 39 (2): 206–­217. https://doi.org/10.1111/j.1467-­2995. 2011.00684.x. Murrell, J. (2018). Perioperative use of non-­ steroidal anti-­inflammatory drugs in cats and dogs. In Practice 40 (8): 314–­325. https://doi. org/10.1136/inp.k3545. Murrell, J.C., Robertson, S.A., Taylor, P.M. et al. (2007). Use of a transdermal matrix patch of buprenorphine in cats: preliminary pharmacokinetic and pharmacodynamic data. The Veterinary Record 160: 578–­583. Norkus, C., Rankin, D., and Kukanic, B. (2015). Pharmacokinetics of intravenous and oral amitriptyline and its active metaboliy nortriptyline in Greyhound dogs. Veterinary Anaesthesia and Analgesia 42 (6): 580–­589.

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6 Regional Anesthesia and Local Blocks Imeldo Laurel1, Jeanette M. Eliason2, Amy Dowling2, Tasha McNerney3,4, and Stephen Niño Cital3,5,6 1

Friendship Hospital for Animals, Washington, DC, USA University of Pennsylvania, Philadelphia, PA, USA 3 The Veterinary Anesthesia Nerds, LLC, Sheridan, WY, USA 4 Mt. Laurel Animal Hospital, Mt. Laurel, NJ, USA 5 Howard Hughes Medical Institute at Stanford University, San Francisco, CA, USA 6 Remedy Veterinary Specialists, San Francisco, CA, USA 2

6.1 ­Introduction Regional anesthesia and local blocks are techniques employed to induce a loss of sensation in a localized area or region of the body, either for pain relief or to facilitate surgical procedures. If local anesthetics are infiltrated locally at the site of surgery this is called local ­anesthesia. If local anesthetics are applied close to nerves or the spinal cord, but are a ­distance away from the surgical site, this is  called regional anesthesia. Sometimes, local anesthetics are also given intravenously as an  adjunctive systemic analgesic and MAC  sparing technique, or to treat arrhythmias. Techniques for regional anesthesia and local  blocks encompass spinal anesthesia, commonly referred to as a subarachnoid block, epidural anesthesia, and nerve blocks. Regional anesthesia/local blocks are highly effective in decreasing the amount of general anesthesia or systemic analgesics needed for patient safety. Several human studies have also found the use of local anesthetics in

surrounding healthy tissue during tumor removal can significantly decrease recurrence and proliferation of several cancer types (Zhang et al. 2021). Most of the drugs used for regional anesthesia/local blocks are relatively cheap, making them not only good practice but also economical. Use of Local Anesthetics Offers Several Benefits 1) Reduced systemic negative effects: Regional anesthesia targets a specific area of the body, which means that the anesthetic agent does not have to circulate through the entire body to achieve its effects. This reduces the risk of systemic side effects and complications associated with general anesthesia or systemic analgesics. 2) Improved pain management: Regional anesthesia is highly effective in managing pain, especially when combined with other pain management strategies. It can provide long-­ lasting pain relief, making it an ideal choice for surgical procedures and postoperative pain management.

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e

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3) Reduced recovery time: Since regional ­anesthesia is not as invasive as general anesthesia, it can lead to a faster recovery time for animals. The animal can stand, walk, and eat shortly after the procedure, which is beneficial for their overall wellbeing. 4) Cost-­effective: Regional anesthesia is often less expensive than increased amounts of general anesthesia and additional systemic analgesic options. 5) Will reduce dependence on using controlled substances. 6) Finally, the techniques used to administer these drugs are relatively easy to perform with proper training.

6.2 ­Current Drug Options for Regional Anesthesia and Nerve Blocks Many different local anesthetic agents are readily available. They all differ in method of use, concentration, onset time, and duration of efficacy. The most widely used regional/local anesthetics are lidocaine, bupivacaine, mepivacaine, and ropivacaine. There is also ­tetracaine proparacaine, and procaine, but those  are primarily used in ophthalmology. Benzocaine is a local anesthetic that is associated with methemoglobinemia in cats and rhesus macaques. It is often found in oral sprays used for endotracheal tube placement. Because

of the high risk of methemoglobinemia, it is not recommended to use this specific drug in animals. Individual nerves exhibit different levels of  susceptibility to regional/local anesthetic agents. In short, narrow-­diameter myelinated sensory fibers, designated as A-­delta fibers, and nerves associated with the autonomic nervous system tend to be more responsive to  regional/local anesthetic agents compared to larger-­diameter pressure fibers (Aβ), motor fibers (Aα), and unmyelinated fibers. This phenomenon clarifies the reason behind the observable differentiation in blockage between sensory and motor nerve groups ­following the administration of various sodium channel-­ blocking agents. Liposomal encapsulated bupivacaine, sold as Exparel® or Nocita®, is also available. These formulations allow the block to last at least 72 hours with some reports in rats and anecdote lasting 96 hours (Kang et  al.  2017). Nocita is the veterinary product labeled for cranial cruciate ligament surgery in dogs and forelimb  onychectomy in cats but has been used widely off-­label for other procedures such as hemilaminectomies, dental blocks, dew-­claw removal, and general surgical incision site infiltration. Caution should be used when using this product off-­label near nerves that control breathing, such as in deep surgical sites near the neck or intrathoracically (Table 6.1).

Table 6.1  Local anesthetic dosing chart.

Sodium channel blocking agent

Dosage (mg/kg) and toxicity risk

Onset time (minutes)

pKa

Protein binding (%)

Lidocaine

1–4, L

1–5

7.9

70

366

60–120

Bupivacaine

1–2, H

2–20

8.1

95

3420

180–480

Ropivacaine

1–2, M

5–20

8.1

95

775

180–480

Mepivacaine

1–3, L

3–5

7.6

75

130

90–180

Lipid solubility

Duration (minutes)

L, Low; M, Medium; H, High. Sodium channel blocking agents with a pKa similar to physiological pH (~7.4) have fasters onset times.

6.2 ­Current Drug Options for Regional Anesthesia and Nerve Block

6.2.1  Mixing Local Anesthetics There has been a long history of mixing various local anesthetic agents such as lidocaine and bupivacaine with the thought that the lidocaine will have a faster onset time, followed by the longer duration of the bupivacaine for longer lasting pain control. Unfortunately, this is not the reality in most of the published studies investigating this technique and it is no longer recommended. In general, mixing local anesthetics does not result in a faster onset and, in fact, it may even reduce the duration (Ribotsky 1996; Sepehripour and Dheansa  2017; Lawal and Adetunji 2009; Lizarraga et al. 2013; Vesal et  al.  2013; Hofmeister  2019; Frank 2012; Almasi et al. 2020).

6.2.2  Adjunctive Agents When using regional blocks, the duration of analgesia can be prolonged by adding other medications such as opioids, dexmedetomidine, steroids, ketamine, and NSAIDs (Meloxicam at 0.2 mg/kg), which did not show postoperative benefits (de O.L. Carapeba et al. 2020), and epinephrine at micro doses. Epinephrine causes constriction of the blood vessels, which slows down the absorption rate and prolongs the effect of the lidocaine. Epinephrine should be avoided in delicate incision sites (thin skin like rabbits or traumatized tissue) or infected tissues because it may impair tissue perfusion and healing. It will also compromise circulation if used on the ears, tail, and digits. Other vasoconstricting agents that offer additional analgesic benefits like medetomidine or dexmedetomidine can also be used. A study done with human patients found that adding dexmedetomidine at (1 mcg/kg) to local anesthetics can prolong the analgesia effect by 3.5–8 hours (Grubb and Lobprise 2020). Preservative-­free (PF) agents, whether that is the local anesthetic or the adjunctive agents, are recommended whenever possible, however long held beliefs that only PF agents could be used for a single, not chronically repeated block, are more than likely safe

(Steagall et  al.  2017). Nevertheless, using a new bottle of a multidose vial of an adjunctive agent is preferred to decrease the chance of bacterial and other forms of contamination. Preservative-­free morphine, or other opioids, added to sodium channel blockers, may enhance postoperative pain control by its synergistic effects, offering more profound analgesia and increasing the duration of efficacy. The full onset time when adding things such as morphine is variable depending on location from a few minutes to several minutes (60 minutes) when used epidurally and can last 6–24 hours (Steagall et  al.  2017). The recommended dosage of morphine is 0.05–0.1 mg/kg and the maximum volume that should be injected is 0.45 ml/kg (Thomas and Lerche 2017). Injectable tramadol (2.5 mg/kg) and butorphanol (0.1 mg/kg) have also been described as adjunctive agents added to local anesthetics with butorphanol showing a superior additive effect (Jang et  al.  2022). It has been shown that buprenorphine can also extend the analgesia effect up to 48–96 hours (Snyder and Snyder 2016). The recommended dosage for buprenorphine injectable is 0.003–0.005 mg/kg (Berg  2020). When using opioids as adjunctive agents there is little concern about competing opioid affinity such as using butorphanol in a local block while ­giving hydromorphone systemically.

6.2.3  Volume Expansion, Onset Time, and Buffering Because most local anesthetics are acidic, they can sting when injected in a conscious patient. Buffering the acidic formulation to minimize the sting has been a common technique that involves adding sodium bicarbonate to the local anesthetic. It has also been suggested that buffering the local anesthetic may decrease onset times. As one can imagine changing the pH of a drug is not without consequence to the efficacy of the drug. It may also lead to precipitation of the solution when the ratio of the buffering agent to local

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anesthetic is inappropriate. In fact, local anesthetics can be less effective in traumatized or infected tissues due to tissue pH changes (Ueno et al. 2008). Lidocaine is superior for tissues that have been traumatized by crushing or maceration, or tissues that are infected, so changing the pH intentionally may be contraindicated. The studies on buffering techniques in both humans and animals are mixed with two notable differences in the studies. In  some studies, the researchers used local anesthetics, most commonly lidocaine, with sodium bicarbonate and epinephrine. The studies with buffered solutions that did not have a significant benefit in onset time or duration, did not contain epinephrine (Guo et al. 2018). In veterinary medicine, epinephrine is not commonly used. It has also been postulated that diluting a local anesthetic with saline or 5% dextrose (D5W) in ratios ranging from 1:1 to 1:10, thereby also increasing the total volume for a local anesthetic, may shorten the onset time of the block. The literature is also mixed. Both techniques, buffering, and dilution (volume expansion), depending on the patient and clinical situation are relatively safe but unpredictable at best making it difficult to recommend (Mosaffa et  al.  2020; Garcia  2015). Interestingly in one study the dilution of a local anesthetic with regular 0.9% saline had the most significant decrease in sting compared to sodium bicarbonate (Zaiac et al. 2012). The authors, when more volume is needed, prefer to use sterile saline at a ratio of one-­part local anesthetic, up to nine-­parts sterile saline.

6.2.4  Maximum Recommended Dose (MRD) The maximum recommended dose (MRD) by definition represents the maximum quantity of drug that can be safely administered during an  appointment in a veterinary case during the  dental procedure (Bassett et  al.  2010). Understanding the drugs and determining the dose before anesthesia is an important role for veterinary nursing staff. Since veterinary

dentistry typically uses multidose vials versus cartridges; calculations are much easier. The clinical staff only needs to know the following information before the procedure: ●● ●●

●●

Concentration of anesthetic drug of choice Maximum dosage recommended for each species Weight of patient

Local anesthetic drugs are configured into percentages. Typically speaking, a 1% bottle of solution would equal 10 mg/ml, or a 10% bottle solution will equal 100 mg/ml. One of the most used sodium channel-­blocking agents in veterinary medicine is 0.5% bupivacaine and contains 5 mg/ml of bupivacaine. The general maximum dosage for bupivacaine is 2 mg/kg. If a 10 kg dog presented in a clinic needed full mouth care the clinical team would use the ­following calculation: Step  1: Figure out the amount of drug in ­milligrams (mg) that can be given. Weight (kg) × max dosage of drug = amount of drug in milligrams (mg) 10 kg × 2 mg/kg = 20 mg Step  2: Divide the amount of drug in milligrams by the concentration of the drug. Milligrams calculated  ÷  concentration (mg/ml) = total volume in milliliters (ml) for 4 quadrants 20 mg ÷ 5 mg/ml = 4 ml total Step 3: Divide the number of millimeters (ml) into four quadrants. This will give you the volume in milliliters to instill in each quadrant. 4 ml ÷ 4 quadrants = 1 ml maximum per quadrant Even though the maximum dose is 1 ml per quadrant, this full volume may not be needed for each block used during the procedure. It is best to start off with half the calculated ­volume per quadrant in case surgeries are long and ­further anesthetic is needed for postoperative analgesia or if the initial injection was not effective. This same technique is also used for local/ regional block calculations where multiple sites

6.2 ­Current Drug Options for Regional Anesthesia and Nerve Block

need to be blocked, such as removing multiple masses on different parts of the body.

6.2.5  Equipment Selection The consumable supplies used to administer regional/local anesthesia in veterinary medicine are minimal and inexpensive. Materials included are local anesthetic drugs of choice, syringes (1–3 ml syringes for most dental, facial, and ophthalmic techniques) (3–20 ml syringes for most other peripheral techniques), hypodermic needles, and loss of resistance (LOR) syringe. More advanced techniques can involve a nerve stimulator, an ultrasound, and specialized needles such as echogenic needles. For dental, facial, ophthalmic, and superficial techniques, or sometimes in tiny animals,

regular hypodermic needles can be used. There are a variety of hypodermic needle sizes and lengths. Needles come in three broad lengths: long, medium, and short. For local anesthesia techniques used in dentistry or facial surgeries, such as inferior alveolar blocks or auriculotemporal blocks, it is recommended to use long (1.5-­in.) hypodermic needles. The shorter length (0.5 in.) is used in the more superficial blocks, such as the mental and maxillary blocks in both small dog and feline breeds. The gauge of the needle pertains to the size of the lumen, which is the hollow bore of the needle. The higher the number the narrower the lumen, the lower the number the wider the lumen is. The larger the gauge, the more rigid the needle typically is. The more rigid the needle, the less chance of deflection (bend) giving Myelinated afferent nerve fiber

LA

Un-ionized

+

Na Voltage-gated Na+ channel

H+ H+

Ionized

LA

+

Na

LA

Extracellular

LA H+

Intracellular

LA +

LA

Na

Action potential generated, allowing pain transmission

H+

H+

Figure 6.1  Mode of action for regional/local anesthetics. Diffusion through the phospholipid bilayer of neurons depends on the un-­ionized concentration of the drug, which is determined by the pKa. Source: Courtesy of Mark Brinker.

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Figure 6.2  A Havel’s® spinal needle with 1 cm depth indicators.

Figure 6.5  A nerve stimulating needle with attached extension set and electrode that connects to the nerve stimulator.

Figure 6.3  A Havel’s® spinal needle with laser etching at the tip to make the tip of the needle more echogenic on ultrasound. Some advanced ultrasound software and needle technology allows for the tip of the needle to be tracked and marked on the ultrasound screen with a red dot.

Figure 6.4  A Braun® glass loss of resistance syringe. The glass syringes can be autoclaved for reuse.

better accuracy to deliver the local anesthetic. For regional/local techniques of the body, it may be advantageous to use needles that have stylets to prevent tissue from clogging the needle during insertion and to maintain rigidity. For regional/local blocking techniques of the body, a variety of syringes and hypodermic needles are needed to draw up and perform the techniques. Other equipment needed includes

Figure 6.6  A Braun® nerve stimulator.

loss of resistance syringes (mainly for epidurals and spinals), regular spinal needles, or spinal needles designed specifically for regional/local blocking techniques. If using a nerve stimulator, you will need specific stimulating needles. Depending on how one plans to perform these techniques, a nerve stimulator and ultrasound with a linear probe are highly recommended;

6.4 ­Dentistry and Facial Blocking Technique

however, many blocks can be performed blindly via anatomical landmarks.

6.3 ­Dental and Facial Regional/ Local Anesthesia Regional/local anesthesia plays a vital role and is a preferred method in the management of dental pain during and after surgical procedures that go beyond routine professional dental cleaning. They aid by blocking pain from teeth, soft tissue, and bone in the anesthetized region making both trauma and surgical experiences more comfortable for the patient while decreasing the reliance of general anesthesia used adding to patient safety. Regional/local anesthesia affects both the sensory and motor nerves and targets the trigeminal nerve (cranial nerve 5/largest ­cranial nerve), which is responsible for the ­sensation of the face. The trigeminal nerve branches out further into the maxillary nerve and the mandibular nerve. Sensory neurons carry signals to the central nervous system (CNS) employing impulses while the motor neurons carry impulses away from the CNS to the tissue or organ of effect. Sodium channel blockers temporarily interrupt or stop neuron activity and nerve impulses thereby decreasing/stopping pain impulses being transmitted to the CNS. When selecting which sodium channel blocking drug to use clinicians must think about the time needed for the drug’s full efficacy and how long the block is anticipated to last after infiltration for pain control during and after the dental procedure. The speed of onset is dependent on the lipid solubility of the anesthetic. Local blocks can be compromised by severe inflammatory responses or increased perfusion (washing away the local anesthetic) at the sight of infection, which can decrease the pH of the surrounding tissue causing the anesthetic block to not be as effective or decrease the duration of efficacy. One must keep in mind that there may be a need to reblock the site if efficacy appears

compromised with careful attention to total dose and toxicity concerns.

6.4 ­Dentistry and Facial Blocking Techniques 6.4.1  Inferior (Caudal) Alveolar Nerve Block (Extraoral/Intraoral) The inferior alveolar nerve block is an extremely effective way to manage pain involving the mandible in both dogs and cats, and other animals. The purpose of the inferior alveolar block is to provide regional anesthesia to the entire ipsilateral mandibular body, teeth, oral mucosa, and lower lip (Lobprise and Dodd 2019). Two techniques known as the intraoral and extraoral are available according to the ­technician’s comfort level and training. Using the extraoral technique reduces the risk  of desensitizing the lingual nerve and trauma caused by chewing during recovery. The extraoral and intraoral techniques have been compared, with the intraoral technique providing higher ­accuracy in proximity to the alveolar nerve (Goudie-­ DeAngelis et al. 2016). Complications and trauma can also occur while administering an inferior alveolar block. Nerves can be damaged during the injection and accidental intravascular injection of the anesthetic can occur. Hematoma formation occurs if digital pressure is not provided for a minimum of 30–60 seconds at the injection site after removing the needle. To avoid desensitizing the lingual nerve and self-­trauma to the tongue, local anesthetic needs to be placed next to the bone, and do not use excessive volumes. Equipment ●● ●● ●● ●●

Local anesthetics Disposable or sterile gloves 1 ml or 3 ml syringe 27-­gauge 1¼ inch or 27-­gauge ½ inch needle

Extra-­oral Technique 1) Draw desired volume of local anesthetic into the syringe.

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2) Intraorally palpate for the mandibular foramen. This foramen is located halfway between the angular process and the last molar dorsal to the ventral notch of the mandible. In cats, it is difficult to palpate, and the location anatomically is less prominent. This foramen for the most part falls in line with the lateral canthus of the eye. 3) Insert the needle facing the bevel to the bone against the periosteum at the lingual cortex. 4) Advance the needle dorsally, to a site one-­ third the height of the mandibular body. While advancing, make sure to avoid puncturing your finger with the needle. 5) Before infiltrating the local anesthetic, draw back on the syringe to verify that it won’t be administered intravascularly. 6) Carefully remove the needle and apply digital pressure, which avoids hematoma formation. It also encourages the spreading of the local anesthetic.

2) Take the nondominant hand and palpate the last molar with the thumb while using the pointer finger to palpate the angular process of the mandible. 3) Using the dominant hand, apply the needle into the oral mucosa lingual distal to the last molar. 4) Insert the needle a little more than halfway (~3/4 of the needle) at a 20–25° angle superior to the mandibular foramen to ensure proper penetration of the nerve. 5) After insertion, aspirate the syringe slowly. When negative aspiration/absence of blood is observed, administer the anesthetic slowly.

Intra-­oral Technique 1) Draw the desired volume of local anesthetic into the syringe.

Figure 6.8  Showing placement of fingers for the extra-­oral technique to help aid in the location of inferior alveolar nerve. Take a non-­dominant hand and palpate the last molar with the thumb while using the pointer finger palpate the angular process of the mandible. Source: Courtesy of Jeanette Eliason.

Figure 6.7  Inferior alveolar foramen is located halfway between the angular process and the last molar dorsal to the ventral notch of the mandible. Source: Courtesy of Stephen Niño Cital.

Figure 6.9  Intra-­oral inferior alveolar technique of needle placement. Source: Courtesy of Jeanette Eliason.

6.4 ­Dentistry and Facial Blocking Technique

Figure 6.10  Inferior alveolar extraoral technique in a skull and cadaver. Source: Courtesy of Stephen Niño Cital.

2) Gently palpate in the buccal vestibule at the region of the mesial root of the second premolar for a small depression to locate the region of needle insertion. 3) Nondominant hand pulls back the frenulum to tighten the bundle. 4) Using the dominant hand, insert the needle at the rostral aspect of the frenulum and advance the needle slightly into the entrance of the foramen in medium to large-­breed dogs. For small-­breed dogs, insert the needle at the region of the foramen. 5) Insert ¼ of the needle tip or less in/at the foramen.

6) Withdraw the needle and massage the region to disperse the anesthetic (Castejon-­ Gonzales and Reiter 2019).

6.4.2  Middle Mental Foramen Nerve Block The middle mental foramen in canine patients is located at the ventral portion of the mesial root of the second mandibular premolar near the labial frenum. In cats, the foramen is located ventral near the labial frenum at the level of the apex of the mandibular canine. Use of this block anesthetizes the mental branch of the mandible nerve as it exits the largest and most rostral of the mental foramina desensitizing the incisors, canine, most rostral premolars, mucosal tissue, and rostral lower lip, and chin anterior to the mental foramen. It is recommended not to insert the needle fully into the foramen due to the likelihood of causing iatrogenic damage to the  neurovascular system. Other complications can include hematoma and bleeding (Reiter and Gracis 2018).

Figure 6.11  Middle mental foramen location in a dog. Located ventral to mesial root of the second premolar near the labial frenum. Source: Courtesy of Stephen Niño Cital.

Equipment ●● ●● ●● ●●

Local anesthetics Disposable or sterile gloves 1 ml or 3 ml syringe 25–27-­gauge ½ inch needle

Middle Mental Foramen Technique 1) Draw desired volume of local anesthetic into the syringe.

Figure 6.12  Middle mental foramen location in a cat. Located ventral near the labial frenum at the level of the apex of the mandibular canine. Source:

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anesthetic, always aspirate to avoid accidental intravascular injection. The nerves can be damaged during the injection and result in persistent neuropathy. There is also the possibility of hematoma formation due to the lack of digital pressure at the injection site. To avoid damage to the eye or globe perforation, make sure to maintain the needle and syringe parallel to the dental arcade. Figure 6.13  Placement of needle for a mental block on an anesthetized canine patient. Source: Courtesy of Jeanette Eliason.

Equipment ●● ●● ●●

6) After insertion, aspirate the syringe slowly. If negative aspiration/absence of blood is  observed, administer the anesthetic gradually. 7) Withdraw the needle and massage the region to disperse the local anesthetic agent.

6.4.3  Infraorbital Nerve Block The infraorbital block provides analgesia to the ipsilateral maxillary oral tissues starting at the injection site, which includes the premolars, canines, and incisors teeth to the midline. This block will also help with the desensitization of the hard palate and is useful for rhinoscopy. Using a longer needle and advancing further into the foramen, a “deep” block could be performed to block a greater surface, but desensitizing the caudal superior alveolar branch of the infraorbital nerve would still be hard to accomplish. The maxillary block is the preferred method to provide analgesia to the fourth premolars and molars. It is important to be aware of all the complications and trauma that can occur from administering an infraorbital block. This block should be performed cautiously in brachycephalic dogs and cats because of the proximity of the ocular orbit to the foramen and the potential for penetrating the globe. The infraorbital artery and vein travel with the nerve within the canal. These should be avoided when injecting a local anesthetic. Before delivery of the local

●●

Local anesthetics Disposable or sterile gloves 1 ml or 3 ml syringe 27 gauge 1½ or ½ inch needle

Infraorbital Nerve Block Technique 1) Draw desired volume of local anesthetic into syringe. 2) Infraorbital foramen can be palpable in two ways: a) Dorsal to the maxillary third premolar b) Palpating the submucosal neurovascular bundle, which is located above the maxillary premolars, and then tracing it caudally to its exit at the infraorbital foramen. 3) Take the syringe and hold the needle parallel to the palate and flat against the maxilla. 4) Insert the needle through the alveolar mucosa, rostral to the opening of the foramen, in a rostral to caudal direction. 5) Advance the needle slowly into the canal, using the medial canthus of the eye as a guide as to how far to advance the needle. 6) Once the needle is within the canal; ­aspirate the syringe slowly if negative aspiration/ absence of blood is observed, administer the anesthetic gradually. 7) Carefully remove the needle and apply digital pressure. 8) Remember not to insert the needle too far or with any force into the foramen in cats and brachycephalic dogs. In cats, the canal is approximately 4 mm long and very minimal in brachycephalic dogs. Due to the proximity of the eye, advancing further into the canal is not recommended.

6.4 ­Dentistry and Facial Blocking Technique

6.4.4  Major Palatine Block: Small Animal

Figure 6.14  Infraorbital foramen located dorsal to the maxillary third premolar with needle placement. Source: Courtesy of Stephen Niño Cital.

Figure 6.15  Infraorbital foramen located in an American beaver to show species anatomical differentiation. Source: Courtesy of Stephen Niño Cital.

The major palatine block is to anesthetize the hard palate, which includes the bone and hard tissues. This block will only affect the structures located lateral to the midline and up to the dental arcade on the side where the local anesthetic was injected. This block may also be useful for rhinoscopy procedures. It is important to be aware that complications and trauma can arise from using the major palatine block. Trauma to the neurovascular bundle can occur if the needle is advanced through its narrow canal. The lack of or insufficient digital pressure at the injection site can cause hematoma formation. Always remember to aspirate before depositing the local anesthetic to avoid accidental intravascular administration. Due to the thickness of the palate epithelium, it makes digital palpation of this foramen impossible. It is very important to remember the locations of the foramen in the dog and cat due to anatomic variation. For the dog, this foramen is located halfway between the midline and the dental arcade at the mesial root of the maxillary first molar. For the cat, this foramen is located halfway between the midline and the dental arcade at the mesial root of the  maxillary fourth premolar. This block is accomplished by working in a rostral to the caudal direction and along the periosteum (Reiter and Gracis 2018). Equipment ●● ●● ●● ●●

Local anesthetics Disposable or sterile gloves 1 or 3 ml syringe 25 or 27-­gauge ½ inch needle

Major Palatine Technique

Figure 6.16  Infra-orbital placement on a cadaver. Source: Courtesy of Jeanette Eliason.

1) Draw desired volume of local anesthetic into the syringe. 2) The needle is angled at 30–45°. 3) Place the needle several millimeters rostral to the foramen and insert through the palatal mucosa.

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4) After insertion, aspirate the syringe slowly if negative aspiration/absence of blood is observed, administer the anesthetic gradually. Note that all dogs and cats are not created equal. Placing the block slightly rostral, will account for anatomic variation in location and will ensure desensitization. 5) Gently remove the needle and apply ­digital pressure at the injection site, which  will also reduce the backflow of the anesthetic.

6.4.5  Caudal Maxillary Block The maxillary block has very similar ­blocking properties to the infraorbital block, in addition to providing analgesia to the maxillary oral tissues starting at the injection site, the premolars, canines, and incisors teeth to the midline. The caudal maxillary block provides analgesia to the incisive bone, palate, gingiva, nasal mucosa, and skin on the same side of the face. Complications can arise from the caudal maxillary block. The maxillary nerve travels along the orbital floor of the eye; needles inserted more than 1–3 mm, depending on breed, can penetrate the orbit, causing vision loss, glaucoma, or enucleation. Equipment ●● ●● ●● ●●

Local anesthetics Disposable or sterile gloves 1 or 3 ml syringe 25 to 27 gauge 1½ or ½ inch needle

Caudal Maxillary Block Technique

Figure 6.17  Showing the location of the palatine foramen and needle placement in the dog. Source: Courtesy of Stephen Niño Cital.

1) Draw the desired volume of local anesthetic into the syringe. 2) Slightly bend the needle 8–10 mm away from the tip at a 45° angle. This will ensure that the needle does not go too far, causing trauma to the orbital region. 3) Breed morphology dependent, insert the tip of the needle approximately 1–3 mm through the oral mucosa perpendicular to the hard palate, immediately caudomedial to the last maxillary molar. 4) After insertion, aspirate the syringe slowly  if  negative aspiration/absence of blood is observed; administer the anesthetic gradually. *Caution must be taken during insertion; penetration too deep can puncture the globe of the eye.

6.4.6  Auriculopalpebral Nerve Block: Motor Blockade of the Eyelid

Figure 6.18  Showing the location of the palatine foramen in the cat. Source: Courtesy of Imeldo Laurel.

Indication The auriculopalpebral nerve is a branch of the facial nerve and innervates the motor nerves of the upper eyelid. Commonly used for ophthalmic exams but is also beneficial for many oph-

6.4 ­Dentistry and Facial Blocking Technique

Figure 6.19  Place the needle immediately caudomedial to the last maxillary molar. Source: Courtesy of Jeanette Eliason.

Figure 6.22  Needle placement for a caudal maxillary block in a skull. Source: Courtesy of Stephen Niño Cital.

Equipment ●● ●● ●●

Figure 6.20  Maxillary nerve block. Source: Courtesy of Jeanette Eliason.

Local anesthetics Needles Syringes

Complications ●●

●●

Ischemic necrosis due to large volumes of local anesthetic Tissue damage from the injection itself

Procedure 1) Insert a 25-­gauge, 5/8-­inch needle containing 3–5 ml of local anesthetic at the dorsal edge of the most dorsal point of the ­zygomatic arch.

Figure 6.21  Needle placement for a caudal maxillary block in a live patient. Source: Courtesy of Jeanette Eliason.

This block is only for motor nerves and produces no loss of sensation. The management of sensory input often involves the application of a supraorbital nerve block or a ring block. See the technique below. The supraorbital nerve, a notable branch stemming from the frontal nerve, traverses the supraorbital foramen situated within the upper orbit.

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●●

Local anesthetic toxicity: Systemic absorption of the local anesthetic used in the block can lead to toxicity, affecting the CNS and potentially causing seizures or other adverse effects. Ocular complications: Complications such as chemosis (conjunctival swelling), ptosis (drooping eyelid), and oculomotor dysfunction may occur.

Procedure Figure 6.23  Needle placement for an auriculopalpebral nerve block in a skull. Source: Courtesy of Stephen Niño Cital.

6.4.7  Retrobulbar Block Indication A retrobulbar block is typically employed for ophthalmic procedures or surgeries involving the eye and its surrounding structures. This technique provides local anesthesia and analgesia to the globe, optic nerve, and adjacent tissues. Common scenarios for the application of ­retrobulbar blocks include ophthalmic surgeries, enucleation (removal of the eye), or other procedures involving the anterior segment of the eye. It aids in minimizing pain and discomfort during these interventions and ensures a more controlled and comfortable environment for the patient. Equipment ●● ●● ●● ●● ●●

Local anesthetics Needles of appropriate size and length Syringes Desired volume of local anesthetic ± Ultrasound for visualization

Complications ●●

●●

●●

Retrobulbar hemorrhage can occur, leading to increased intraorbital pressure and potential compression of the optic nerve. The optic nerve can be inadvertently injured during the administration of the block, resulting in impaired vision or blindness. Damage to blood vessels in the retrobulbar space may cause bleeding and hematoma formation.

1) Ensure that the animal is adequately anesthetized, and aseptically prepare the injection site for the procedure. 2) Bend the needle tip at approximately a 20° angle to conform to the orbit. 3) Insert the needle at the 7 o’clock ­position, below the eyelid, ensuring it traverses along the bony orbit to avoid puncturing the globe or blood vessels. Direct the ­needle along the floor of the orbit, then redirect dorsally and toward the nose to reach the apex of the orbit. A slight popping sensation may be felt upon piercing the orbital fascia. Redirect the needle slightly dorsally and nasally toward the orbital apex. 4) The globe will rotate caudally until the conjunctival sac is breached, then it will rotate back to a standard position. 5) If any resistance is encountered, stop immediately and withdraw the needle slightly. 6) Aspirate for blood, fluid, or resistance. If none is present, inject a test dosage (0.5 ml or less) of local anesthetic. If there is no resistance and the patient remains stable, proceed with the rest of the injection over 30 seconds.

6.4.8  Frontal Nerve (Supraorbital Foramen) Block The frontal nerve is the branch of the trigeminal nerve that provides sensory innervation to the medial two-­thirds of the upper eyelid. This block is most utilized during eyelid surgery and can be used for a transfrontal craniotomy when done bilaterally.

6.4 ­Dentistry and Facial Blocking Technique

Figure 6.24  Needle placement required for retrobulbar injection performed via the ITP technique in an anesthetized dog. Source: Courtesy of Stephen Niño Cital.

Figure 6.26  Inferior retrobulbar technique in a cat. Source: Courtesy of Tasha McNerney.

Complications ●● ●●

Hypersensitivity reactions to medications Possible ocular or eyelid trauma due to poorly restrained or improperly sedated patients

Procedure 1) Patient is placed under general anesthesia or sedation. 2) Palpate the supraorbital foramen (located as the zygomatic process of the frontal bone widens, dorsal to the medial canthus of the eye).

Figure 6.25  A skull that has been sectioned through an eye and orbit to illustrate the approximate path of needle placement required for retrobulbar injection performed via the ITP technique. Notice that the tip of the needle terminates in the intraconal fat. Source: Specimen preparation done by Dr. Wencke Reineking and Elias Godoy, Stanford University.

Equipment ●● ●● ●●

Local anesthetics 25-­gauge needles 3-­ml syringes

Figure 6.27  Frontal nerve block technique on a dog skull. Source: Courtesy of Stephen Niño Cital.

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condition that is  often treated by surgical removal of the ear  canal, known as total ear  canal ablation (TECA) in combination with lateral bulla ­osteotomy (LBO) (Stathopoulou et al. 2018). Equipment ●●

●●

Figure 6.28  A patient resting comfortable post transfrontal craniotomy with a frontal nerve block. Source: Courtesy of Stephen Niño Cital.

3) 1 ml of 2% lidocaine HCl is injected over the opening to the supraorbital foramen, in which the frontal nerve exits.

6.4.9  Auriculotemporal Block + Greater Auricular Block For procedures involving the ear canal and pinna, an auriculotemporal block targeting the great auricular (auricularis magnus) and the  auriculotemporal nerve (auriculotem­ poralis) has been recognized to block ­sensory innervation. These patients present with chronic otitis externa, a chronically painful

●●

●● ●●

1 mg/kg bupivacaine (or local anesthetic of your choice) ±0.075 mg/kg morphine or 0.003 mg/kg buprenorphine A 25-­gauge 5/8 inch needle for most cats and a 22 gauge 1–1½ inch needle for dogs Syringes ± Ultrasound for visualization

Complications ●● ●●

●●

Nerve or vessel injury. lingual nerve blockade leading to desensitization of the tongue which can lead to ­subsequent self-­mutilation lesions. Potential laceration of the parotid gland.

Procedure 1) Clip and prepare the area using aseptic technique. 2) Palpate the area overlying the TMJ with the patient in lateral recumbency.

Figure 6.29  Needle placement for auriculotemporal block (GAn = Greater auricular nerve, Jv = Jugular vein, B = Tympanic bulla, ATn = auriculotemporal nerve, TMJ = temporomandibular joint, C1 = Cervical vertebrae 1). Source: Layne and de Miguel Garcia (2019) / with permission of John Wiley & Sons.

6.5 ­Common Regional and Local Anesthetic Techniques: Less Specifie

3) In performing an auriculotemporal nerve block in veterinary practice, the needle is introduced into the skin located between the rostral aspect of the ear canal and the dorsal aspect of the most caudal part of the zygomatic arch. Once the needle is advanced halfway between the skin and the bone, the solution is administered at that specific site. The needle should be oriented toward the TMJ and at the level of the masseteric margin during the infiltration (Stathopoulou et al. 2018). 4) For a greater auricular nerve block, the procedure involves inserting the needle into the skin ventral to the wing of the atlas and caudal to the ear canal. The needle is then advanced into the subcutaneous tissue, and the solution is deposited at the site situated caudal to the vertical ear canal. 5) Aspirate to confirm you are not in a vessel, and slowly inject.

6.5 ­Common Regional and Local Anesthetic Techniques: Less Specified All the techniques described in this section will require the following equipment: some variation will be present depending on the type of block. ●● ●● ●● ●● ●● ●● ●● ●● ●●

Clippers Antiseptic skin prep Sterile gloves Local anesthetic ± additive Syringe for local anesthetic ± Nerve stimulator ± Ultrasound ± Hypodermic needle ± Spinal or nerve stimulating needles

All techniques in this section should be done after shaving and prepping for aseptic technique. It is highly encouraged to wear sterile gloves if one is touching the needle or skin. When performing these techniques, standard practice is to aspirate once at the point of interest, followed by a slight rotation and another aspiration attempt, ensuring one is not in a blood vessel.

6.5.1  Intraperitoneal Lavage Technique for Dogs and Cats Indicated during feline and canine abdominal procedures. For intraperitoneal analgesia during ovariohysterectomy, the local anesthetic is splashed into each ovarian ligament and on the neck of the uterus before excision of ovarian pedicles and uterus during ovariohysterectomy. The technique is performed under general anesthesia to avoid laceration or puncture of abdominal organs and peritonitis. One of the factors that might contribute to the failure of IP local anesthesia for postoperative pain management after abdominal surgeries may be related to the inadequate distribution of local anesthetics throughout the visceral and peritoneal surface due to inadequate volume (Brioschi et al. 2023). Procedure 1) Administer the local anesthetic immediately after making the incision or upon completing the abdominal procedure, just before closure. 2) Instill the drug directly into the abdomen through the incision, essentially bathing or lavaging the peritoneal cavity. Standard closure procedures are then followed, leaving the local anesthetic within the abdomen. a) It is worth noting that lavaging just before closure with adequate volume may be more beneficial. There is a risk local anesthetic will be absorbed by gauze sponges used during the procedure if the lavage is performed at the start of the procedure.

6.5.2  Incisional Line Block Wound infiltration involves the injection of a local anesthetic directly into the surgical field and is popular in human and veterinary medicine due to its relative simplicity, safety, and low cost. It is used before surgical incision or after surgery and before skin closure. This block is most commonly used during closure after abdominal pro­cedures such as ovariohysterectomy or skin incisions during procedures such as a laceration repair.

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Procedure Line Block Before Incision 1) Insert the needle subcutaneously after a sterile prep. 2) Aspirate. 3) Inject enough local anesthetic to produce a noticeable bleb. 4) Remove the needle and reinsert at the edge of the bleb. 5) After aspiration, inject more local anesthetic to extend the bleb. 6) Repeat the process until the length of the incision has been blocked. Incisional Line Block Before Closing Incision 1) The incisional block is done in a sterile manner by the surgeon. Someone must pass the needle and syringe aseptically to the surgeon to prevent contamination. This is most commonly performed using liposomal encapsulated bupivacaine; however, any local anesthetic can be used. 2) Insert the needle at one end on the midline of the incision before closing the skin. 3) After aspiration for blood, inject local anesthetic in a fanlike manner to block subcutaneous and muscular tissues. If this is being performed on the abdominal body wall, inject local anesthetic down to the peritoneum. Remove the needle and reinsert a slight distance away, reinjecting local anesthetic in a fanlike manner. Repeat until the area under the whole incision has been infiltrated.

Figure 6.30  Incisional block before closing using Nocita®. Source: Courtesy of Stephen Niño Cital.

6.5.3  Circumferential Block Circumferential ring block is an extremely easy, inexpensive, and effective way to manage postoperative pain. Injections are made just above the carpal bend on the top side of the paw and just above the accessory carpal pad on the underside. This four-­injection technique provides regional nerve block sufficient to eliminate pain for up to 8 hours post-­surgery. In cats, the dosage is 1 ml of 0.5% bupivacaine per 5 kg of body weight divided equally among the injection sites. Sterile saline can be added to achieve sufficient coverage for smaller cats. In dogs, up to 2 ml per 5 kg of body weight can be used. Procedure 1) Draw the full volume of the local block into the syringe. 2) Tent skin horizontally across the top of the forepaw just above the carpal bend. 3) Insert the needle subcutaneously across the paw to cover the entire top surface. 4) After aspirating, slowly withdraw the needle while injecting ¼ total volume to form a line. 5) Repeat on the underside of the forepaw just above the accessory carpal pad. 6) Change the needle. 7) Repeat the procedure on the opposite side. 8) Massage forepaw gently to distribute local anesthetic.

6.6 ­Regional and Local Blocks of the Thorax and Abdomen 6.6.1  Intercostal Blocks The intercostal nerve block is easily performed with training and knowledge of anatomy. It  can be performed blind or via ultrasound. It blocks portions of the thoracic wall, inferior to where the block was performed. Intercostal nerve blocks can provide comparable and, in  some cases, better analgesia to epidural and  systemic opioid administration. This nerve block also resulted in improved ventilator function compared with the systemic administration of opioids in canine patients after thoracotomy (Otero and Portela 2018).

6.6 ­Regional and Local Blocks of the Thorax nd AAdomen

Indications ●● ●● ●●

●●

Lateral thoracotomies Thoracic wall tumor removal Thoracic drain placement and chest tube placement It can also be indicated in the pain management of rib fractures, thoracic wall trauma, postoperative and flail chest.

Equipment ●● ●●

± Ultrasound machine with linear transducer Easy access to a detailed veterinary anatomy resource such as a book or the internet

Landmarks ●●

Caudal border of the rib

Potential Complications ●● ●● ●●

Intrapleural injections Pneumothorax Local anesthetic toxicity

Procedure (Blind) 1) Blocks are performed in two to three spaces cranial and caudal to the affected area. The nerves are located on the caudal aspect of the rib behind the vein and artery. 2) Place the needle just caudal to the rib. If you hit the rib with the needle, walk the needle off the caudal edge. 3) Aspirate for blood. 4) Inject local anesthetic.

Figure 6.31  Injection sites for intercostal technique. Source: Courtesy of Mark Brinker.

Procedure via Ultrasound (Otero and Portela 2018) 1)  Adjust the reading depths to 1–3 cm depending on the size of the animal. 2)  Adjust the ultrasound gain and apply gel or alcohol to enhance acoustic coupling. 3)  Identify the target intercostal spaces. 4)  Identify the desired intercostal space by counting from the last rib either manually or using the ultrasound probe. 5)  The ultrasound scan should be performed over the proximal third of the rib, ideally close to the angle of the rib. 6)  Center the target intercostal space in the middle of the ultrasound screen. 7)  Introduce the needle in-­plane at the caudal border of the transducer and advance it through the intercostal muscles in a cranial direction until the tip is located just above the parietal pleura. 8)  Confirm that the tip of the needle is not in a vessel or the chest. 9)  Slowly inject the local anesthetic in the space between the parietal pleura and the internal intercostal muscle. 10)  Repeat this technique for every intercostal to be blocked (Otero and Portela 2018).

Figure 6.32  Placement of transducer and needle for an intercostal nerve block. Source: Courtesy of Amy Dowling.

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Landmarks ●●

The seventh to the tenth intercostal spaces

Potential Complications ●● ●● ●●

Pneumothorax Catheter dislocation Diaphragmatic paralysis (when the phrenic nerve is blocked and using bilateral tubes)

Procedure

Figure 6.33  Sonographic image of the needle at the caudal aspect of the rib for infiltration of local anesthetic. Source: Courtesy of Stephen Niño Cital.

6.6.2  Interpleural Block Intrapleural analgesia is a technique that distributes local anesthetic into the intrapleural space. This technique can help provide pain relief following post-­traumatic thoracic pain and for treating chronic pain disorders. It can improve a patient’s ventilation and can be used as a longer-­ term form of analgesia when a catheter is put in place so that repeated dosing can take place. Some literature suggests this may also be useful for pancreatitis-­related pain. Reasons to choose this technique over an intercostal blockade are ease of administration, ability to re-­dose and provide analgesia following a median sternotomy. It is a relatively safe block with anatomy knowledge and practice. It is usually performed blind with the palpation of the landmarks being the seventh to the tenth intercostal spaces (Campoy and Read 2013). Equipment ●●

●●

Over-­the-­needle catheter (14–20  gauge, 2 inch) or other indwelling catheter or chest tube. A three-­way stopcock is required to enable repeated injection of local anesthetic and to evacuate air from the thoracic cavity so that iatrogenic pneumothorax can be prevented.

1) Place the catheter in the ninth intercostal space on the mid lateral aspect of the thorax. 2) Aspirate. 3) Inject lidocaine (1.5 mg/kg) first. The patient may momentarily vocalize because the lidocaine may sting, but the onset of the lidocaine block is rapid. 4) Inject the bupivacaine (1.5 mg/kg) next. If bupivacaine is injected first, the patient will vocalize for 15–25 minutes, the amount of time it takes for onset. 5) This procedure can be repeated every 3–6 hours. If injecting through a chest tube, a small amount of saline can be used to flush the local anesthetic into the chest. 6) The local anesthetic may be diluted with saline to minimize the initial stinging sensation. 7) Place the patient in a posture to facilitate block. a) Roll the patient onto its back so the local anesthetic flows into the paravertebral gutters to block nerves before entering the spinal cord. This is most common in patients under anesthesia because they are easily moved. b) Place the patient in an upright position. This is most common in awake patients. c) Position the patient onto the affected side. d) Position the patient on the unaffected side. e) If intrapleural anesthesia does not seem to work, attempt to alter the patient’s position to change the distribution of the local anesthetic.

6.6 Region l nd Loc lBlocksof theThor ax nd AAdomen

6.6.3  Intratesticular and Spermatic Cord Block Intratesticular block is extremely easy to ­perform and, depending on the anesthetic agents administered, can provide up to 8 hours of postoperative pain relief for patients undergoing castration by anesthetizing the spermatic cord. The addition of opioids to local blocking agents will extend the duration of pain relief (Moses 2013). Procedure 1) Shave testicles and inguinal area and perform sterile prep. 2) Isolate and stabilize one testicle and then insert the needle from the caudal pole along the long axis of the testicle. The tip of the needle should be in the middle of the testicle or in the cranial 1/3. 3) Isolate the spermatic cord and insert the needle into the cord. It is important to draw back first before injecting to ensure you are not in a vessel. 4) Inject, expecting firm back pressure, while withdrawing the needle. 5) Expect to use about ½ or less of the drug volume per testicle until the testicle becomes turgid. 6) Repeat for another testicle (Stein 2013). Any leftover blocking agent can be utilized to perform an incisional line block.

Figure 6.35  Needle placement into the spermatic cord. Source: Courtesy of Stephen Niño Cital.

Figure 6.36  Needle depth placement into the testicle. Source: Courtesy of Mark Brinker.

6.6.4  Sacrococcygeal Block

Figure 6.34  Needle placement into the testicle of a dog. Source: Courtesy of Stephen Niño Cital.

This technique is very useful for providing analgesia for procedures that involve the tail, perineum, caudal urogenital tract, and anus. It can be used for other hind limb procedures if your patient’s lumbar-­sacral space is difficult to palpate because of obesity or trauma. It is relatively safe, fast, and easy to perform. One benefit to this technique over an L7-­S1 epidural is that the patient will still have motor function if an appropriate dose is used.

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Indications ●●

●● ●● ●●

Perineal region –– Anal gland surgery –– PU surgery –– Cystoscopy –– Vaginoscopy –– Tail wound –– Tail amputation –– Urinary catheter placement for blocked cats –– Deobstipation Middle and caudal abdomen Hind limb procedures When a L7-­S1 epidural is not possible (trauma, obesity skin infection at site)

Techniques ●● ●●

Blind Nerve stimulator

Equipment ●●

●● ●●

Spinal, hypodermic, or nerve stimulating needle ± Nerve stimulator Local anesthetics ± adjuvants

Procedure via Nerve Stimulator 1) Repeat the first four steps from the blind technique. 2) Attach your positive lead of the nerve stimulator to the patient and turn the current to 1 mA. 3) Have an assistant attach the nerve stimulator needle. 4) Have your assistant then attach the syringe with anesthetic to the nerve stimulator needle. 5) As you advance you should see contractions of the muscles and the distal third of the tail without contraction of the perineal muscles. 6) Decrease your mA as low as you can until you don’t get a twitch. If the tail is still twitching below 0.2 mA adjust your needle because you are too close to the nerve. 7) Once you have a twitch at 0.5–0.7 mA you can have your assistant slowly inject the drugs if there is no resistance. Dose ●●

0.1–0.2 ml/kg total volume of local anesthetic ± adjuvant

Potential Complications ●● ●● ●●

Nerve damage Urinary retention (with morphine use) Local anesthetic to toxicity

Procedure (Blind) 1) Place the patient in sternal or lateral recumbency, with the hind limbs pulled forward cranially. 2) Clip the targeted area (S1 to coccygeal). Move the tail up and down to assist in finding the space between S1 and the first coccygeal vertebra. 3) At a 45–90° angle insert the needle caudal to the spinous process and advance it until it enters the epidural space. 4) There is minimal resistance in this space because of the thinning of the ligamentum flavum caudal to the LS space. 5) Once you have verified you are in the correct location, aspirate and then inject the local anesthetic.

Figure 6.37  Placement of needle in a cat for a sacrococcygeal block. Source: Courtesy of Trish Farrey and Tasha McNerney.

6.6 Region l nd Loc lBlocksof theThor ax nd AAdomen Epidural Skin Subcutaneous Muscle

L6

Sacrococcygeal Block

L7

Sacrum

C1

C2

Spinal cord Intrathecal space Epidural space Interspinous ligament

Figure 6.38  Placement of needle for epidural and sacrococcygeal block. Source: Courtesy of Mark Brinker.

6.6.5  Epidural Neuraxial anesthesia is the administration of anesthetic medication into the epidural or subarachnoid space leading to loss of sensory and/or motor function. It covers the procedures caudal to the region of the twelfth or thirteenth ribs (Ko and Inoue 2013). When using a local anesthetic there may be loss of motor depending on dosing. If an additive is used, such as morphine, the analgesic effects of the epidural could last up to 24 hours. There may be urinary retention if morphine is added, which can be resolved by either expressing the patient’s bladder or placing a urinary catheter (Otero and Portela 2018). There are a variety of drugs and combinations of drugs that are used in epidural anesthesia. Most commonly a local anesthetic such as bupivacaine is combined with an opioid such as preservative-­free morphine. Factors to consider include desired duration, the area to be affected, and the importance of retaining motor function. The most common epidural blockade drugs used are lidocaine at 3–5 mg/kg with a 5-­ to 10-­minute onset and 1-­ to 4-­hour duration. Mepivacaine at 3–4 mg/kg with a 5–10-­minute onset and 2-­to 4-­hour duration. Bupivacaine at 0.5–1 mg/kg with a 10–15-­minute onset and 2–4-­hour duration. Ropivacaine at 1–2 mg/kg

with a 10-­ to 15-­minute onset and 1-­ to 3-­hour duration. See (Table  6.2) for other common drugs used for epidurals. Tissues You Will Go Through (Otero and Portela 2018) ●● ●● ●● ●● ●● ●●

Skin Subcutaneous tissue Muscle Supraspinous ligament Interspinous ligament Ligamentum flavum or interarcuate

Indications ●● ●●

Caudal abdominal surgeries Hind limb procedures (including but not limited to) –– Pelvic fractures –– Total hip replacement –– Femoral fractures –– Perineal surgery

Equipment ●●

●●

Spinal needle (22 gauge) is usually big enough in most small animals but the length can vary depending on the size of your patient. Sterile gloves.

149

Table 6.2  Commonly used and recommended epidural anesthetics and analgesics in dogs. Source: Steagall et al. (2017). Dose (mg kg–1)

Final volume (mL kg–1) injected into the LS epidural space

Onset time (min)

Duration of analgesia (h)

5.0

0.25

4–6

1

Duration of motor blockade 60–120 min

0.5% Bupivacaine

0.5–1.0

0.2–0.25

5–15

>2

Duration of complete motor blockade and ataxia was 65 and 240 min, respectively. May be prolonged with 0.75% bupivacaine. Complete motor blockade may not be observed at 0.25%

0.5% Levobupivacaine

0.5–1.0

0.2

5–15

1–1.5

0.75% Ropivacaine

1.65

0.22

7–15

1.5–2.5

Opioids Morphine PF

0.1

0.1 for abdominal and pelvic procedures; 0.25 for thoracic procedures

45–90

12–24 for pelvic limb and abdominal procedures at 0.1 mL kg–1; 5–6 for thoractomy procedures at 0.25 mL kg–1

Reduced minimum alveolar concentration (MAC) by 30% and minimized CV depression from inhalant. Potential for urinary retention and pruritus

0.004

Reduced risk for urinary retention

Drug

Local anesthetics 2% Lidocaine with 1:200,000 epinephrine

Buprenorphine

Comments

Duration of complete motor blockade and ataxia was 30 and 180 min, respectively. Complete motor blockade may not be observed at 0.25% Duration of motor blockade 90–150 min

0.2

methadone > hydromorphone > oxymorphone > morphine Adapted from (Mathews 2008) adverse effect can be avoided by giving either drug IV (Text Box 8.1). Buprenorphine is the only partial agonist opioid used in veterinary medicine, although the actions of buprenorphine are debated in Chapter  5. Historically it is accepted that buprenorphine binds to the mu opioid receptor but only partially activates it and therefore provides less analgesia than the agonist opioids. However, at appropriate dosages it can provide adequate analgesia for a laparotomy procedure. The downside is that it has a longer peak onset time of 30–45 minutes regardless of the route of administration. This prolonged onset time to peak effects makes it less desirable to use for an emergent C-­section, but if it can be administered early then it is appropriate for an elective C-­section or use in a pregnant patient. A single injection may provide analgesia for 6–8 hours. Butorphanol is a mixed agonist/antagonist opioid that only provides approximately 30–60 minutes of analgesia. It stimulates the kappa receptor (kappa agonist) and blocks the mu receptor (mu antagonist). For this reason, it  only provides mild visceral analgesia. Butorphanol does not provide adequate ­analgesia for a major abdominal procedure (Robertson and Moon 2003; Grubb et al. 2020).

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8.1.2.3  Alpha-­2 Agonists

This drug class includes xylazine, detomidine, romifidine, medetomidine, dexmedetomidine, and a new mixed drug combination known as Zenalpha (medetomidine and vatinoxan). These drugs provide sedation, muscle relaxation, analgesia, and minimum alveolar concentration (MAC) sparing effects. They have the added benefit of being reversible with atipamezole. They have a profound effect on the cardiovascular system causing a transitory hypertension and a reflex bradycardia with a subsequent drop in cardiac output-­exception Zenalpha. Uterine blood flow is not auto regulated, which means a decrease in cardiac output directly impairs uterine blood flow and fetal oxygen delivery. Uterine motility is also increased, which may be detrimental during pregnancy but is less of a concern during a C-­section. Profound sedation is typically not warranted in a pregnant animal unless the animal is displaying fearful or aggressive behavior. An older study by Moon (2000) identified xylazine as a perioperative risk factor that adversely affected neonatal survival. This study unfortunately did not indicate the dosages of xylazine utilized. More recent studies performed with medetomidine and dexmedetomidine during C-­sections show that low dosages of either agent complement anesthesia and do not negatively impact maternal or neonatal survival. A retrospective study on medetomidine showed that 7 mcg/kg IV greatly reduced the propofol dosage required for induction and sevoflurane concentration required for maintenance (De Cramer et  al.  2017). A study conducted by Groppetti et al. (2019) showed that 2 mcg/kg IV dexmedetomidine also decreased the induction dosage of propofol and isoflurane concentration. Furthermore, this study demonstrated the absence of dexmedetomidine in the amniotic fluid, suggesting that the placenta was an effective barrier against exposing the neonate to longer exposure times. Based on the data obtained from these recent studies, low

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dosages of medetomidine or dexmedetomidine can be considered for use during pregnancy and C-­sections when the temperament of the dam would benefit from additional sedation to augment handling and restraint. 8.1.2.4  Dissociative Agents

Ketamine and tiletamine (found in combination with zolazepam) are the most commonly used dissociative drugs used in veterinary medicine. Ketamine is commonly used with a benzodiazepine for induction. If used alone, ketamine can increase uterine tone that results in a subsequent decrease in uterine blood flow (Jimenez Lozano 2013). A study conducted by Moon-­Massat and Erb (2002) showed that ketamine/benzodiazepine combinations did not impact overall puppy survival but did decrease puppy “vigor.” The prolonged depressant effects on the neonates required more vigorous resuscitative efforts to achieve spontaneous ventilation. The residual depressant effects on the neonates make these agents less desirable when compared to the other induction drugs. The use of sub-­anesthetic dosages (0.3–1 mg/kg) of ketamine as an adjunct analgesic during pregnancy or for C-­section procedures has not been studied in veterinary medicine. Sub-­ anesthetic IV ketamine dosages have been used in human medicine to complement analgesia during C-­sections with no ill effects on the mother or fetus (Behdad et al. 2013). 8.1.2.5  Local and Regional Blocks

Numerous studies have evaluated the use of an epidural for C-­sections in veterinary patients and found it to be an excellent option to mitigate neonatal complications such as respiratory depression, minimize systemic analgesic use and improve the overall comfort of the dam through all phases of anesthesia (Luna et  al.  2004; Robertson 2016; Aarnes and Bednarsky 2015). Antończyk and Ochota (2022) showed that a lidocaine epidural combined with isoflurane maintenance allowed for lower isoflurane concentrations, produced higher Apgar scores at 5-­ and 20-­minutes following birth, and had no negative impact on umbilical cord blood gas results.

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Ideally, the epidural should be performed immediately after induction so that it will benefit the dam during the actual procedure. Alternatively, it can be performed after the procedure is complete but before the dam is recovered. The combination of preservative-­ free (PF) morphine and PF lidocaine is commonly used if it is performed right after induction whereas PF morphine and saline are used if it is performed post-­procedure. Omitting the local anesthetic for a post-­procedure epidural ensures the dam will not experience prolonged paresis during the recovery period. An epidural will provide excellent analgesia for the dam and often negates the use of systemic analgesics in the immediate postoperative period. When performed prior to the procedure it helps keep the inhalant concentration low (MAC sparing) and will decrease the likelihood that additional boluses of opioids are needed intra-­operatively. During pregnancy, the epidural venous plexus becomes engorged. This is likely due to an increase in intra-­abdominal pressure and collateral circulation. The epidural venous distension causes the epidural and cerebrospinal fluid spaces to decrease in size. To avoid excessive cranial migration when local anesthetics are used, the total volume administered for an epidural should be decreased by 25–35%. Several animal studies have demonstrated a decreased onset time and more intense blockade when local anesthetics are administered epidurally during pregnancy (Otero and Campoy  2013). Hypotension may occur after placement of the epidural with local anesthetics due to sympathetic blockade. The administration of IV crystalloid fluids helps to offset this adverse effect. Utilizing an epidural (local anesthetic ± PF morphine) as the sole anesthetic technique for a C-­section in dogs and cats is not recommended. The only advantage of considering this technique is to minimize fetal exposure to anesthetic drugs. However, the pharmacokinetics of the drugs used today make it difficult to justify this advantage. Furthermore, there are numerous disadvantages to the mother and potential harm

8.1 ­Introductio

to the fetuses prior to delivery. Most dogs and cats will not tolerate being placed in dorsal recumbency and holding still for a prolonged period while fully conscious. The mother will likely require deep sedation and/or significant manual restraint for the procedure. Deep sedation requires high doses of sedatives which pose a higher risk to the neonates compared to low concentration of inhalant since systemic drugs must undergo hepatic metabolism. Multiple people may need to assist in manual restraint of the mother, which is a poor use of resources. The mother is not intubated which means there is no protected airway. Even with the laryngeal reflexes intact while awake they are still at a high risk of regurgitation and aspiration when placed in dorsal recumbency due to the weight of the gravid uterus. The mother may still respond to pressure, traction, and/or manipulation of the uterus even with deep sedation and an epidural. If the mother becomes restless or fights manual restraint after the procedure has started, then general anesthesia may still be needed which means that intubation will need to occur in dorsal recumbency. This is significantly more difficult than intubation in sternal or lateral recumbency. Higher dosages of local anesthetics will be needed to achieve complete motor blockade, which could cause some residual motor deficits after the procedure is complete. Many clinicians are hesitant to consider an epidural during a C-­section due to the time it takes to perform this task. Although there is a learning curve, once proficient, this task only takes a few minutes to perform. However, if an epidural is not performed, there are some alternative techniques to consider. One option is to perform an incisional line block in conjunction with intraperitoneal lavage (Kalchofner Guerrero et  al.  2016; Grubb  2022). An incisional line block is placed in the subcutaneous tissue along the location of the skin incision prior to the start of the surgical procedure. It can be placed prior to the final aseptic prep or placed by the surgeon once they are gowned and gloved. Intraperitoneal lavage involves simply squirting the local anesthetic into the abdomen to bathe the serosal surfaces of the

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organs within the abdominal cavity. This technique is generally performed immediately prior to closing the body wall so that the local anesthetic is not absorbed in sponges or washed away if the abdomen is flushed with saline. Steagall et al. (2019) reviewed the supporting evidence for these techniques in both cats and dogs. The review concluded that these two techniques are superior to either technique alone and play a beneficial role as part of a multimodal analgesic protocol for any abdominal procedure. The longer acting local anesthetics such as 0.5% bupivacaine or 0.5% ropivacaine are generally used for these procedures. Table 8.1 indicates the maximum dosage for the local anesthetics. It is extremely important to ensure the total volume of local anesthetic does not exceed the maximum dosage to prevent systemic toxicity. One fourth of the volume is typically used for the incisional block and the remaining volume is placed intraperitoneally. If more volume is required, then the local anesthetic can be diluted with equal volume saline. Alternatively, lidocaine can be used for the incisional block prior to the skin incision and bupivacaine liposome suspension (Nocita®) can be used prior to closing the skin layers. The use of Nocita in this manner is off label. Nocita is administered as an infiltrative block using a moving needle technique to inject the suspension into all tissue layers prior to closing the incision and provides 72 hours of analgesia. Nocita can also be used in conjunction with opioids. A short-­acting agonist opioid such as fentanyl is administered IV combined with a PF morphine epidural would provide adequate analgesia during the C-­section and Nocita Table 8.1  Maximum dosage for local anesthetics. Bupivacaine 4 mg/kg (dogs); 2 mg/kg (cat) Lidocaine 8 mg/kg (dogs); 4 mg/kg (cat) Ropivacaine 4 mg/kg (dogs); 2 mg/kg (cat) Mepivacaine 5 mg/kg (dogs); 3 mg/kg (cat) Grubb and Lobprise (2020) / John Wiley & Sons / CC BY 4.0.

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administered at closing would provide analgesia postoperatively. A Transversus Abdominis Plane (TAP) block is another alternative to the epidural that can be used for abdominal procedures. In humans the TAP block is commonly performed after a C-­section to enhance the postoperative recovery period particularly when traditional analgesic methods such as spinal injection with opioids or systemic NSAIDs are not utilized or contraindicated. This technique is best performed utilizing ultrasound guided assistance to visualize the different muscle layers of the abdomen. The block is performed in lateral or dorsal recumbency and must be performed bilaterally to be effective for a midline incision. It only provides analgesia for somatic pain associated with incision of the abdominal wall. This block is not effective against visceral pain (Cavaco et al. 2022). Cavaco et al. (2022) showed that bupivacaine administered as a two-­point bilateral TAP block was effective at reducing the need for rescue analgesia within the 6-­hour postoperative period in dogs undergoing ovariectomy. Campoy et  al. (2022) demonstrated that the combination of bupivacaine and dexmedetomidine administered via TAP block preoperatively provided adequate postoperative analgesia for dogs undergoing ovariohysterectomy. Interestingly, this study concluded that the use of liposomal bupivacaine in the TAP block did not appear to provide any added benefit to the duration of postoperative analgesia. Although there are no studies specifically looking at the benefits of TAP block in dogs or cats undergoing a C-­section, the results of the above studies suggest that it would be a valuable tool to consider as part of a multimodal analgesic protocol for these procedures.

8.2 ­Postoperative Analgesia It is imperative that postoperative pain be addressed in the mother and adequately treated when present. One of the main goals

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during recovery is to get the neonates nursing as soon as possible. A study performed by Traas (2008) showed that inadequate pain management and/or poor recovery after a C-­section will likely contribute to decreased milk production. A single injection of an opioid can be used in the immediate postoperative period if the dam is showing signs of pain. As long as the mother is deemed normovolemic, an NSAID injection followed by a short course (1–3 days) of oral NSAIDs will help provide analgesia by decreasing inflammation in the postoperative period.

8.3 ­Anesthesia and Analgesia Case Management for a Cesarean Section Regardless, if the procedure is emergent or elective, all efforts should be made to minimize the mother’s stress and anxiety level during the preoperative period. Keeping the noise level to a minimum and dimming the lighting in the room may help assist with keeping the dam calm during the preparation phase. Ideally, an IV catheter should be placed prior to any drug administration. IV catheterization should be considered mandatory to facilitate drug administration, fluid therapy, perioperative management (e.g., additional analgesia or supportive therapy) and emergency intervention (if warranted). The cephalic vein will be most accessible for the anesthetist during the procedure, but if the dam struggles with restraint, the saphenous vein may be the better option to minimize stress. If the dam resists restraint for IV catheter placement, then consider IM premedication with an alpha-­2 agonist and opioid to decrease her overall stress level. Utilizing minimal restraint, the mother should be clipped for the abdominal procedure prior to any drug administration, if possible. In women, the supine position (e.g., on their back) is known to cause compression of the caudal vena cava and aorta due to the weight of the gravid uterus. This could potentially cause a significant decrease in cardiac output

8.3 ­Anesthesia and Analgesia Case

to the uterus and compromise perfusion to the fetus. There are veterinary studies in dogs that showed there is no difference in blood pressure when a pregnant patient is placed in lateral, lateral tilt (10–15°) or dorsal recumbency (Robertson  2015). The likely explanation for this is that the bicornuate uterus of the dog allows the horns to lie on either side of the major vessels when placed in dorsal recumbency. While the risk for compromising blood flow to the fetuses appears to be less in dogs it is still recommended to minimize the time the patient spends in dorsal recumbency during the prep phase. This is especially important for mothers with a large litter size or abnormally large fetuses and giant breeds of dog. An initial prep of the abdomen should be done prior to moving into the operating room. In addition, the site for Doppler placement (e.g., metacarpal artery) and epidural should be clipped and the epidural injection site surgically prepped. To decrease the overall anesthesia time, C-­section patients are often walked to the operating room once all personnel are present and know their prospective role. The patient is premedicated with the opioid IV and placed on the operating table. Pre‑oxygenation should occur for at least 3–5 minutes prior to induction as long as the dam does not struggle or fight having the mask placed over her nose. Pre‑oxygenation will fill the functional residual capacity of the lungs with a higher percentage of oxygen than room air and will prolong the onset of hypoxemia. Ideally, there should be two people dedicated to induction and intubation of the dam while one person is ready to place the epidural immediately after induction. The surgeon should be gowned in and have the instrument table set up prior to induction. A rapid sequence induction with the IV opioid first followed by the injectable anesthetic agent (e.g., propofol or alfaxalone) is the preferred method to induce general anesthesia as it offers the quickest way to gain control of the airway. Induction agents should be titrated to effect until intubation can be achieved. Once intubated, the patient is placed on 100% oxygen and the inhalant of choice (isoflurane or sevoflurane). After the

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Management for a Cesarean Sectio

induction process has started a final sterile prep of the epidural site should be completed with the patient in sternal recumbency. The epidural can then be performed while the anesthetist is obtaining vital signs and attaching the monitoring equipment to the patient. After the epidural has been placed, the patient is moved to dorsal recumbency, and a final sterile prep is performed on the surgical site. With an appropriately sized team it is common to only have about 15–20 minutes lapse between induction, epidural placement, and delivery of the first puppy or kitten. Most references say that “time is of the essence” for these procedures and delivery of the neonates should occur as quickly as possible in order to minimize fetal exposure to the anesthetic drugs and decrease adverse side effects (e.g., fetal hypoxia and respiratory depression). Several studies have looked at fetal drug exposure compared to different delivery times. Interestingly, no evidence exists that shows a rapid delivery time is associated with a better outcome for the neonates. In fact, one study showed that neither a long anesthesia time (>45 minutes) nor long delivery time (>10 minutes) had any negative effect on puppy mortality (Moon-­Massat and Erb  2002). However, many theriogenologists will say that delivering the neonates is only the first step in this process. Neonatal resuscitation and care of the newborns is the second step. For this reason, it is still desirable to have as short of time as possible between induction and delivery of the neonates. There should be a secondary team of individuals handling neonatal resuscitation as the puppies or kittens are delivered. A warming box should be present to place the neonates once they are deemed healthy and have an appropriate Apgar score. Once the surgical procedure is complete the dam should be moved to a recovery area with adequate padding and heat support. The neonates should be encouraged to begin nursing as the mother is recovering from anesthesia. It is imperative that the team stay with the mother until she has made a full recovery and is conscious enough to properly care for the neonates (Table 8.2).

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Table 8.2  C-­section protocols. Elective C-­section, healthy ASA I or II patient *Place IV catheter first Premedication ●●

0.1 mg/kg hydromorphone IV

Or ●●

0.3–0.5 mg/kg methadone IV

Or ●●

0.25–0.5 mg/kg morphine (Slowly IV)

Induction (titrate to effect) ●●

2 mg/kg alfaxalone IV

Or ●●

4 mg/kg propofol IV

Maintenance ●●

Isoflurane or sevoflurane

Epidural (before surgery) ●●

0.1 mg/kg PF morphine

●●

1 ml/4.5 kg Lidocaine to a total volume of 0.22 ml/kg when combined with PF morphine

Postoperative ●●

4.4 mg/kg carprofen SQ

●●

DOGS ONLY: Acetaminophen 5–15 mg/kg PO or IV

���������������������������������������������������������������� Elective C-­section, healthy ASA I or II patient with aggressive temperament *Give premedication IM Premedication ●●

0.1 mg/kg hydromorphone IM or 0.3–0.5 mg/kg methadone IM or 0.25–0.5 mg/kg morphine IM

+ ●●

5 mcg/kg dexmedetomidine IM

Induction (titrate to effect) ●●

2 mg/kg alfaxalone IV

Or ●●

4 mg/kg propofol IV

Maintenance ●●

Isoflurane or sevoflurane

Epidural (before surgery) ●●

0.1 mg/kg PF morphine

●●

1 ml/4.5 kg Lidocaine to a total volume of 0.22 ml/kg when combined with PF morphine

Postoperative ●●

4.4 mg/kg carprofen SQ

●●

DOGS ONLY: Acetaminophen 5–15 mg/kg PO or IV

����������������������������������������������������������������

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8.4 ­Pain

Management for Neonates and Pediatric

Table 8.2  (Continued) Emergent C-­Section due to dystocia, ASA III Patient *Place IV catheter first Premedication ●●

1–5 mcg/kg fentanyl bolus IV followed by 0.1–0.3 mcg/kg/min fentanyl CRI

Induction (titrate to effect) ●●

2 mg/kg alfaxalone IV

Or ●●

4 mg/kg propofol IV

Maintenance ●●

Isoflurane or sevoflurane

Epidural (before surgery) ●●

0.1 mg/kg PF morphine + 1 ml/4.5 kg Lidocaine to a total volume of 0.22 ml/kg when combined with PF morphine

Or ●●

Line block with 1–2 ml bupivacaine prior to surgery + 2 mg/kg (dog), 1 mg/kg (cat) bupivacaine intraperitoneal lavage prior to closing

Postoperative ●●

±4.4 mg/kg carprofen SQ depending on hydration status

●●

DOGS ONLY: Acetaminophen 5–15 mg/kg PO or IV

8.4 ­Pain Management for Neonates and Pediatrics

8.4.1  Insulting the Neonatal Pain Pathways

Like a pregnant mother, neonatal and pediatric patients require different considerations for analgesia due to their unique physiology. In this chapter which is consistent with the World Small Animal Veterinary Associations definitions, a neonate is considered to be (0–2 weeks of life), infant (2–6 weeks) weanling (6–12 weeks), and juvenile (3–6 months). This distinction is made to highlight the ­metabolic changes that occur during these periods of maturation. Differences in hepatic, renal, and cardiovascular physiology should be considered when selecting analgesics. Additionally, the importance of neonatal pain pathway development and the negative effects caused by acute pain or insufficient analgesia will be explored here.

The idea that pain experienced in infancy is inconsequential to the development of the neonatal patient has been debunked with numerous studies starting as early as 1980 (Perry et  al.  2018). Unfortunately, it has remained a common practice in many hospitals, both human and veterinary, to forgo analgesics in the face of mounting evidence outlining the long-­term negative side effects of untreated neonatal pain. Data pertaining to behavioral, physiological, and developmental changes have been collected in human and animal models and clearly demonstrate the long-­term negative effects of neonatal pain following amputation and tissue trauma, both very common occurrences in both veterinary and human neonatal medicine (Perry et  al.  2018). Research in animal physiology suggests that experiencing nociceptive stimuli

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that would equate to pain in an adult can have lasting effects beyond the neonatal period. These studies have shown that pain producing nociceptive stimuli in early life can lead to ongoing decreased pain thresholds in the affected areas, indicating developmental changes in the spinal cord. Early exposure to stress might also weaken the immune response, leading to slower wound healing and possibly a higher risk of infection. Untreated pain in the neonatal period could result in increased pain sensitivity, weakened immune function, more avoidance behaviors, and heightened social alertness. Even though an individual might not retain a conscious recollection of early painful experiences, the body seems to record these events, as indicated by the long-­term impacts mentioned earlier. For human infants born preterm or with low to extremely low birth weight, as well as for newborns undergoing standard medical procedures like heel pricks or circumcision, these experiences could significantly influence their development. This highlights the importance of avoiding neonatal pain when possible and, when unavoidable, ensuring it is recognized and managed with as much care as pain in adults (Anand et  al.  1999; Page 2004). 8.4.1.1  NMDA Receptors

Research demonstrates that the activation of NMDA receptors early in life plays a role in exacerbating hyperalgesia (Miranda et  al. 2014). One associated cause of hyperalgesia is amputation, a common procedure performed in veterinary patients, especially in the form of tail docking in dogs. Specifically, the formation of traumatic neuromas at the site of amputation can result in chronic neuropathic pain, sometimes called “phantom limb pain.” The tissue changes associated with neuroma formation have been observed as early as 4 weeks following tail docking in piglets, with all piglets developing neuromas 8  weeks following amputation (Sandercock et al. 2016). This has been reflected in dogs on a smaller scale when

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examined for self-­inflicted tail stump mutilation following docking (Gross and Carr 1990). In one study involving human amputee patients, sensitized neuromas were attributed as the cause of pain in nearly 50% of individuals (Rajput et al. 2012). 8.4.1.2  Cutaneous Receptors

Cutaneous receptors are responsible for the detection of mechanical, thermal, and nociceptive stimuli. In neonates, cutaneous receptive fields (CRF) are expansive. Insults to these receptors can occur for a number of reasons: mechanical trauma, metabolic disorders, autoimmune diseases, and viral infections (Stucky and Mikesell 2021). When disrupted, nociceptive signaling from cutaneous receptors can result in allodynia and chronic pain conditions. Knowing that neonates have a substantially larger CRF, it is imperative that pain at this level is treated to reduce incidence of allodynia and subsequent behavioral problems. This is why local anesthetics, including EMLA™ creams and lidocaine, whether administered locally or intravenously, can provide effective pain relief. A study has recommended a mixture of 2% lidocaine and sodium bicarbonate to reduce pain when infiltrating tissues (Rodriguez and Jordan 2002). The recommended dosages vary based on age and species, with a lower dosage for neonates due to the immaturity of their peripheral nerves, rather than concerns about potential side effects (Figure 8.2) (Mathews 2008).

8.4.2  Treatment of Pain in Neonatal and Pediatric Patients 8.4.2.1 Opioids

Opioid analgesics are the most suitable first choice for the treatment of pain in the neonatal and pediatric veterinary patient. Fentanyl is an ideal agonist opioid to consider due to its rapid onset, short duration, ease of titration, and lowered risk of adverse effects than those seen with morphine (Luks et al. 1998). Buprenorphine is an excellent choice for longer-­lasting analgesia

 ­Reference

8.4.2.2  Nonsteroidal Anti-­inflammatory Drugs (NSAIDs)

NSAIDs, such as carprofen, meloxicam, and deracoxib, should be avoided in neonates under 6 weeks of age due to their underdeveloped kidneys and liver, particularly in cases of hemodynamic instability (shock, hypovolemia). Harris (2000) explains that some NSAIDs target COX-­2, responsible for pain and inflammation, but COX-­2 also plays a critical role in nephron maturation. It’s important to note that the embryologic kidney does not achieve complete maturation until approximately 3  weeks after birth, with normal function occurring around 6–8 weeks of age, as highlighted by Horster et  al. (1971) and WSAVA (2020). 8.4.2.3  Alpha-­2 Agonists Figure 8.2  A 2-­week-­old puppy with a cleft palate and lip that is about to undergo a surgical correction. Local anesthetics and buprenorphine were used for analgesia.

and can be administered by oral transmucosal means or intranasally. Buprenorphine does not offer as much sedation as the agonist opioids and produces minimal respiratory depression. Neonates typically necessitate lower dosages compared to slightly older puppies, emphasizing the age-­related differences (Berde and Sethna 2002). It is recommended to administer lower dosages of opioids in patients less than 5 weeks of age, with room to titrate higher if needed to adequately manage pain.

There is anecdotal evidence that suggests pediatric patients less than 8 weeks of age may not have abundant peripheral alpha-­2 receptors to initiate the initial vasoconstriction and reflex bradycardia that is commonly seen in adult patients. Based on clinical experience, low dosages of alpha-­2 agonists (1–2 mcg/kg) play a beneficial role in providing sedation, analgesia, and MAC sparing effects while maintaining normal heart rate and blood pressure. More research is needed in this patient population to confirm these anecdotal findings. 8.4.2.4  Local and Regional Blocks

Nearly every technique described in adult patients can be applied to neonatal animals, however low-­end dosing is recommended, such as half the dosage/volume suggested in adults (WSAVA 2020).

­References Aarnes, T.K. and Bednarsky, R.M. (2015). Cesarean section and pregnancy. In: Canine and Feline Anesthesia and Co-­Existing Disease (ed. L.B.C. Snyder and R.A. Johnson), 299–309. USA: Wiley Blackwell.

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Aarnes, T.K. and Murdock, M.A. (2022). Cesarean section and pregnancy. In: Canine and Feline Anesthesia and Co-­Existing Disease, 2e (ed. R.A. Johnson, L.B.C. Snyder, and C.A. Schroeder), 566–584. USA: Wiley Blackwell.

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Almeida, V.T., Uscategui, R.A., Silva, P.D. et al. (2017). Hemodynamic gestational adaptation in bitches. Ciência Rural 47 (7): https://doi. org/10.1590/0103-­8478cr20160758. Anand, K.J., Coskun, V., Thrivikraman, K.V. et al. (1999). Long-­term behavioral effects of repetitive pain in neonatal rat pups. Physiology & Behavior 66 (4): 627–637. https://doi.org/10.1016/s0031-­9384(98)00338-­2. Antonczyk, A. and Ochota, M. (2022). Is an epidural component during general anaesthesia for caesarean section beneficial for neonatal puppies’ health and vitality? Theriogenology 187: 1–8. Behdad, S., Hajiesmaeili, M.R., Abbasi, H.R. et al. (2013). Analgesia effects of intravenous ketamine during spinal anesthesia in pregnant women undergone caesarean section; a randomized clinical trial. Anesthesiology and Pain Management 3 (2): 230–233. Berde, C.B. and Sethna, N.F. (2002). Opioids in the management of pain. In: Pediatric Anesthesia, 4e (ed. J.J. Ziegler, F.E. Rives, and R.J. Levy), 671–687. Lippincott Williams & Wilkins. Campoy, L., Martin-­Flores, M., and Boesch, J. (2022). Transverse abdominis plane injection of bupivacaine with dexmedetomidine or a bupivacaine liposomal suspension yielded lower pain scores and requirement for rescue analgesia in a controlled, randomized trial in dogs undergoing elective ovariohysterectomy. American Journal of Veterinary Research 83 (9): AJVR.22.03.0037. https://doi.org/ 10.2460/ajvr.22.03.0037. Cavaco, J.S., Otero, P.E., Ambrósio, A.M. et al. (2022). Analgesic efficacy of ultrasound-­ guided transversus abdominis plane block in dogs undergoing ovariectomy. Frontiers in Veterinary Science 9: 1031345. https://doi.org/ 10.3389/fvets.2022.1031345. De Cramer, K.G.M., Joubert, K.E., and Nothling, J.O. (2017). Puppy survival and vigor associated with the use of low dose medetomidine premedication, propofol

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induction and maintenance of anesthesia using sevoflurane gas-­inhalation for cesarean section in the bitch. Theriogenology 96: 10–15. Ferrari, D., Lundgren, S., Holmberg, J. et al. (2022). Concentration of carprofen in the milk of lactating bitches after cesarean section and during inflammatory conditions. Theriogenology 181: 59–68. Freeman, S.L., Russo, M., and England, G.C. (2013). Uterine artery blood flow characteristics assessed during oestrus and the early luteal phase of pregnant and non-­ pregnant bitches. The Veterinary Journal 197 (2): 205–210. https://doi.org/10.1016/ j.tvjl.2013.02.015. Groppetti, D., Cesare, F.D., and Pecile, A. (2019). Maternal and neonatal wellbeing during elective C-­section induced with a combination of propofol and dexemedetomidine: how effective is the placental barrier in dogs? Theriogenology 129: 90–98. Gross, T.L. and Carr, S.H. (1990). Amputation neuroma of docked tails in dogs. Veterinary Pathology 27 (1): 61–62. Grubb, T. (2022). Local analgesic techniques for gonadectomy: focus on intraperitoneal lavage. dvm360 magazine 53(7): 32. https://www. dvm360.com/view/ local-­analgesic-­techniques-­for-­gonadectomy-­ focus-­on-­intraperitoneal-­lavage Grubb, T. and Lobprise, H. (2020). Local and regional anaesthesia in dogs and cats: overview of concepts and drugs (part 1). Veterinary Medicine and Science 00: 1–9. Grubb, T., Sager, J., Gaynor, J.S. et al. (2020). 2020 AAHA anesthesia and monitoring guidelines for dogs and cats. Journal of the American Animal Hospital Association 56 (2): 59–82. https://doi.org/10.5326/jaaha-­ms-­7055. Harris, R.C. (2000). The role of cyclooxygenase-­2 in renal disease. Journal of Nephrology 13 (Suppl 3): S3–S10. Horster, M.F., Braun, G.S., Matignon, M., and Manin, S. (1971). Postnatal development of renal function in the dog. Nephron 8 (4): 285–296. Jimenez Lozano, M.A. (2013). Updates on anesthesia for non-­obstetric and obstetric

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surgery during pregnancy. Clinical Theriogenology 5 (3): 190–200. Kalchofner Guerrero, K.S., Campagna, I., Bruhl-­Day, R. et al. (2016). Intraperitoneal bupivacaine with or without incisional bupivacaine for postoperative analgesia in dogs undergoing ovariohysterectomy. Veterinary Anaesthesia and Analgesia 43: 571–578. KuKanich, B. and Wiese, A.J. (2015). Opioids. In: Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones (ed. K.A. Grimm, L.A. Lamont, W.J. Tranquilli, et al.), 207–226. Wiley. Luks, A.M., Krenke, B.E., and McCabe, M.A. (1998). Fentanyl in neonates undergoing cardiac surgery: efficacy and pharmacokinetics. The Journal of Thoracic and Cardiovascular Surgery 115 (4): 780–787. Luna, S.P., Cassu, R.N., Castro, G.B. et al. (2004). Effects of four anaesthetic protocols on the neurological and cardiorespiratory variables of puppies born by caesarean section. The Veterinary Record 154: 387–389; 2004. Mathews, K. (2008). Analgesia in small animals. Veterinary Clinics of North America: Small Animal Practice 38 (6): 1181–1207. Mathews, K. and Sinclair, M. (2018). Analgesia and anesthesia for pregnant cats and dogs. In: Analgesia and Anesthesia for the Ill or Injured Dog and Cat (ed. K.A. Mathews, M. Sinclair, A.M. Steele, and T. Grubb). Wiley. Miranda, A., Mickle, A., Bruckert, M. et al. (2014). NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation. European Journal of Pharmacology 5 (744): 28–35. https://doi. org/10.1016/j.ejphar.2014.09.034. Moon, P.F., Erb, H.N., Ludders, J.W. et al. (2000). Perioperative risk factors for puppies delivered by cesarean section in the United States and Canada. JAAHA 36 (4): 359–368. Moon-­Massat, P.F. and Erb, H.N. (2002). Perioperative factors associated with puppy vigor after delivery by cesarean section. JAAHA 38 (1): 90–96.

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Otero, P.E. and Campoy, L. (2013). Epidural and spinal anesthesia. In: Small Animal Regional Anesthesia and Analgesia (ed. L. Campoy and M.R. Read), 227–259. Wiley-­Blackwell. Page, G.G. (2004). Are there long-­term consequences of pain in newborn or very young infants? The Journal of Perinatal Education 13 (3): 10–17. https://doi.org/ 10.1624/105812404X1725. Perry, M., Tan, Z., Chen, J. et al. (2018). Neonatal pain: perceptions and current practice. Critical Care Nursing Clinics of North America 30 (4): 549–561. Raffe, M.R. (2015). Anesthetic considerations during pregnancy and for the newborn. In: Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones (ed. K.A. Grimm, L.A. Lamont, W.J. Tranquilli, et al.), 708–719. John Wiley & Sons. Rajput, K., Reddy, S., and Shankar, H. (2012). Painful neuromas. Clinical the Journal of Pain 28 (7): 639–645. https://doi.org/10.1097/AJP. 0b013e31823d30a2. Robertson, S.A. (2015). Anesthesia Considerations & Techniques for Caesarian Section. World Small Animal Veterinary Association World Congress Proceedings. Robertson, S. (2016). Anaesthetic management for caesarean sections in dogs and cats. Practice 38: 327–339. Robertson, S.A. and Moon, P.F. (2003). Anesthetic management for cesarean section in bitches. Veterinary Medicine 675–696. Rodriguez, C. and Jordan, P. (2002). Infiltrative anesthesia in cats and dogs. Veterinary Clinics of North America: Small Animal Practice 32 (3): 791–807. Sandercock, D.A., Smith, S.H., Di Giminiani, P., and Edwards, S.A. (2016). Histopathological characterization of tail injury and traumatic neuroma development after tail docking in piglets. Journal of Comparative Pathology 155 (1): 40–49. Schneider, M., Kuchta, A., Dron, F., and Woehrle, F. (2015). Disposition of cimicoxib in plasma and milk of whelping bitches and in their puppies. BMC Veterinary Research

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11: 4e9. https://doi.org/10.1186/ s12917-­015-­0496-­4. Steagall, P.V.M., Benito, J., Monteiro, B. et al. (2019). Intraperitoneal and incisional analgesia in small animals: simple, cost-­ effective techniques. Journal of Small Animal Practice, Capsule Review. British Small Animal Veterinary Association. Stucky, C.L. and Mikesell, A.R. (2021). Cutaneous pain in disorders affecting peripheral nerves. Neuroscience Letters 765: 136233. https://doi. org/10.1016/j.neulet.2021.136233. Traas, A.M. (2008). Surgical management of canine and feline dystocia. Theriogenology 70: 337–342.

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Vilar, J.M., Batista, M., and Perez, R. (2018). Comparison of 3 anesthetic protocols for the elective cesarean-­section in the dog: effects on the bitch and the newborn puppies. Animal Reproduction Science 190: 53–62. WSAVA (2020). Neonatal and pediatric patients. https://wsava.org/wp-­content/uploads/ 2020/01/Neonatal-­and-­pediatric-­patients.pdf (accessed 12 January 2023). Yazdy, M.M., Desai, R.J., and Brogly, S.B. (2015). Prescription opioids in pregnancy and birth outcomes: a review of the literature. Journal of Pediatric Genetics 4: 56–70. https://doi. org/10.1055/s-­0035-­1556740.

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9 Analgesia in the Emergency and Critical Care Setting Heather Ann Scott 1 and Rachel Stauffer 2 1 2

Ethos Veterinary Emergency and Referral Center Hawaii, Honolulu, Hawaii, USA Veterinary Emergency Group Powhatan, VA, USA

9.1 ­Introduction As a part of the fundamental five freedoms in animal welfare, pain management is an essential part of treatment in an emergency (ER) or  intensive care unit (ICU); particularly “Freedom from Discomfort,” “Freedom from Pain, Injury or Disease,” and “Freedom from  Fear and Distress.” (Mellor  2016) Left untreated, pain can have significant physiological and psychological effects on patient outcomes in an emergency and critical care (ECC) setting, including delayed healing and poor patient outcomes. Alleviation of pain can reduce patient stress and anxiety, and vice versa. The ECC veterinary technician must be prepared to assess and evaluate pain in the critically ill patient as an essential part of their role. They must advocate for, understand the modality of, and evaluate the effects of pain management interventions as a part of providing well-­rounded high-­quality nursing care. Providing safe, effective, efficient pain management is not only possible but also an ethical obligation. This chapter will discuss in further detail the importance of immediate pain ­control in emergent and critically ill patients, in addition to the use of multimodal pain management, case-­based strategies, and the pain

management aspect of Kirby’s rule of 20 as applied to an ECC setting.

9.2  ­Treating Pain in the Emergency and Critical Care Veterinary Patient When considering treatment for the emergency veterinary patient, the focus is typically on treating pain that is acute in nature. Please see Chapter  3 for the definition of “acute” and  “chronic” pain. Many studies underline and  support the evidence that pain is underrecognized and undertreated in all areas of  ­veterinary medicine, in ECC, it’s largely under-­recognized and undertreated due to often having multiple comorbidities, overlooking the nature of painful stimuli induced by common procedures done in ECC (invasive device ­placement, venipuncture, etc.) and inconsistencies in proper assessment. This is hypothesized to be the result of multiple factors such as staffing shortages, individual perceptions/­misconceptions of pain associated with ­pro­cedures and diseases, limited knowledge of pharmacokinetics/pharmacodynamics, ­inadequate pain assessment training, post-­ graduation tenure, and misconceptions related

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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to side effects (Rousseau-­Blass et  al.  2020; Simon et  al.  2017). Executing adequate pain management in the emergency veterinary patient is also commonly met with reluctance due to the unique complications of many emergent and critically ill patients. Clinicians often fear that a patient will decline or expire with the use of pain control when a patient is unstable. However, if acute pain is left untreated or poorly managed, it may result in more serious and long-­lasting sequelae such as an increased inflammatory response hastening the progression of a condition and/or chronic pain (Rousseau-­Blass et  al.  2020). While not commonly considered in veterinary medicine the prevalence of “ICU psychosis” or “intensive care delirium” is a condition described in human medicine that could conceivably occur in animals and is exacerbated by pain. ICU ­psychosis/delirium is a disorder described as increased anxiety, paranoia, disorientation, and even aggression of patients spending multiple days in a hospital setting. Moreover, because of the long-­lasting physiological consequences of untreated pain,  this common misconception can lead to ­prolonged hospitalizations and poorer patient outcomes. With these considerations in mind, treating pain in ECC patients, particularly patients presenting in the emergency room setting, should be expedient, individualized, and multi-­modal whenever possible. The continued research and development of a wide variety of pain management techniques utilizing pharmaceutical and nonpharmaceutical interventions help provide a synergistic approach to overcoming the challenges of treating acute pain, even in the most unstable patients. Multimodal analgesia addresses pain via various mechanisms of action in the nociceptive pathway allowing for lower dosages of drugs that then produce fewer less than desirable effects whilst increasing the efficacy of other drugs that would otherwise be inadequate when used alone. Patients presenting with critical illness often  have cardiovascular instability, multiple comorbidities, and/or concurrent preexisting

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conditions (commonly masked by compensatory mechanisms), in conjunction with several maladaptive mechanisms at play during presentation. Given these challenges, opioids are often the first line of treatment for ECC pain management due to their potency, versatility, reversibility, and safety margin in treating acute pain. When evaluating options for pain management, the disease/injury, onset of action of the medication, route of available administration, and duration of pain management should be considered (see Table 9.1).

9.3  ­Evaluating Pain in ER and ICU Patients When evaluating pain in an ECC patient from a nursing care standpoint it is imperative to initiate pain management care quickly, systematically, and consistently. Using a standardized pain assessment scale can help facilitate this (see Chapter 4). Because several pain scales exist, it is pertinent to understand where they are most applicable and effective on a case-­by-­case basis. Pain scales notably have varying degrees of validation, so utilizing a validated pain scale is highly encouraged whenever possible. Furthermore, acute, and chronic pain scales should not be used interchangeably. The use of appropriate, validated, and species-­specific pain scales can help decrease subjectivity, human bias, and inaccuracies during pain evaluation (Epstein et al. 2015; Maíra et al. 2021). In an ER setting, the utilization of a simple pain scale such as the CSU pain scale, while not fully validated, can still be useful because it can be used quickly in urgent situations to help provide expedient pain management when indicated. For cats, the feline grimace scale is not only validated for acute pain assessment, but it is also user-­friendly and efficient once personnel are trained. Clinicians should lean toward providing more pain management when the status is questionable as there are more detrimental effects providing inadequate

Table 9.1  Commonly used pain management in the ECC setting. Route of administration

Onset of action (min)

Canine and feline: 0.2–0.5 mg/kg

IV, IM, OTM, SC (at higher dosages, but not recommended)

Canine: 0.05–0.15 mg/kg

Drug

Dosage range

Methadone

Hydromorphone

Frequency

Pain level

Case examples

Comments

1–5 IV or 10–20 IM

2–4 hours

Moderate to severe

Trauma, urethral obstruction, back injury, ocular emergencies, abdominal pain

Minimal vomiting and GI effects compared with hydromorphone and morphine administration. Higher dosages can be used for OTM administration, whereas other dosages are given IV. Potential extension of duration of action has been seen when combined with fluconazole administration.

IV, IM, SC (may cause vomiting)

1–5 IV or 10–20 IM

4–6 hours

Moderate to Severe

Trauma, postoperative surgical pain.

Vomiting and nausea commonly occur with IM and SC route. Opioid-­induced hyperthermia occurs more frequently with the use of higher doses -­particularly in feline patients. Increases in temperature are generally mild to moderate and are self-­limiting (0.04 mg/ kg can be used like a full mu opioid.

SC administration of this formulation is not recommended at dosages less than 0.03 mg/kg for anything greater than minor pain

SC

Up to one hour

24 hours

Mild to moderate

Post operative surgical pain in

Studies in dogs for dosing anticipated to last 24 hours like in cats were unfavorable. This formulation can be used at the dosages, frequency and routes of administration mentioned in the standard formulation for both dogs and cats.

Canine and feline: Bolus 2–5 mcg/ kg + CRI 1–50 mcg/kg/h

IV

1–2 minutes IV

20–30 minutes (single bolus injection without maintenance CRI)

Moderate to severe

Critical illness of undetermined nature, origin, trauma, surgical patients (as CRI),

If the intended use is for inhalant anesthesia sparring effects. Synergistic effects if co-­administered with other anesthetic agents. Caution with co-­administered serotonergic agents due to increased risk of serotonin syndrome. Caution with CYP3A4 inhibitors (e.g. diltiazem), which may increase plasma levels of fentanyl. Pharmacokinetics are unaffected by renal or hepatic insufficiency.

Canine and feline: 4–12 mcg/kg/h

IV CRI

30 seconds to 2 minutes IV

10–15 minutes (single bolus injection without CRI)

Moderate to severe

Critical illness of undetermined origin, trauma, surgical patients (as CRI)

No bolus is required, half potency of fentanyl. Ideal opioid for liver disease patients

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Oxymorphone

Canine 0.05–0.4 mg/kg IV q2–4h

IV, IM

5–10 minutes

2–4 hours

Moderate to severe

Trauma, urethral obstruction, back injury, ocular emergencies, abdominal pain

Does not cause the histamine release associated with morphine May cause bradycardia, increased sensitivity to sound, and decreased ability to thermoregulate.

Feline 0.2–0.5 mg/kg IV q3–4h Butorphanol

0.2–0.4 mg/kg

IV, OTM, IM, SC (not recommended)

10–15 minutes

1–2 hours

Mild

Can be used as sedation for procedural techniques, may be used as an adjunct to other nonopioid pain medications

More suitable for sedation or mild pain, not suitable for moderate to severe pain

Ketamine

0.5 mg/kg IV 0.002 mg/kg/min IV CRI (hospitalization) 0.01 mg/kg/min IV CRI (surgery)

IV, IM, IN, OTM, SQ

15–30 seconds IV 10 minutes IM

5–30 minutes

Moderate to severe (best as an adjunct)

Spinal trauma, prolonged sustained bone or tissue injury without appropriate pain management

Excellent complement to multimodal pain management and anesthesia protocols. Decreases windup and central sensitization. Used as a mainstay treatment for pain vacation protocols.

Dexmedetomidine

0.001–0.005 mg/kg

IV, IM, SQ (not recommended)

~20 minutes in dogs and cats

40–90 minutes

Moderate to severe (as an adjunct)

Post operative acute pain management adjunct. Adjunct for local regional blocks, visceral pain. Micro dosages can be used in blocked cats as an adjunct without decreasing CO.

Acts on the presynaptic membrane, inhibits the release of norepinephrine inducing hyperpolarization and inhibiting pain signals to the brain. Reduces opioid consumption, can decrease onset, and prolong nerve blocks. Reduces MAC of isoflurane. Has neuroprotective properties. Avoid use in severely anemic patients, patients with pericardial effusion, and pulmonary hypertension patients.

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(Continued )

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Table 9.1  (Continued) Route of administration

Onset of action (min)

Frequency

Pain level

Case examples

Comments

Canine and feline: 2–20 mg/kg

PO

30–60 minutes

8–12 hours

Mild to moderate (as an adjunct to multimodal pain management). May have opioid sparing effects and help with sleep quality.

Neuropathic pain management and adjunct to post operative pain management

Binds to voltage-­gated calcium channels that are upregulated in response to a noxious insult to inhibit calcium influx, inhibits the release of excitatory neurotransmitters. May be beneficial as an adjunct pain management option prior to surgical procedures and continued post operatively, should not be used as a sole pain management medication, or considered a treatment for acute pain. Can have anti-­anxiety effects in both canine and feline patients.

3–5 mg/kg

PO

1–2 hours

8–12 hours

Mild to moderate (as an adjunct to multimodal pain management). May have opioid sparing effects and help with sleep quality.

Neuropathic pain management and adjunct to post operative pain management

Voltage gated Ca2+ channel antagonist. Binds to α-2δ subunit to produce antiepileptic and analgesic actions. Studies suggest perioperative use and follow up TID use postoperatively.

Drug

Dosage range

Gabapentin

Pregablin

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9.4  ­Nursing Care and the Role of Pain

pain management versus providing adequate analgesia. In an ICU setting, the use of a more in-­depth pain scale such as the Modified Glasgow composite pain scale (canine vs feline) should be considered, the use of the feline grimace scale can be used in both the ER and ICU environment. A patients’ pain status should be continually reevaluated, being sure to first observe without disturbing or entering the patient’s housing or close to it, and then assessing while manipulating or palpating the animal noting responses to stimuli and physical interaction. Subtle changes can occur from hour to hour. The patient’s willingness to walk or stand, appetite, ability to comfortably rest, and mentation should also be considered as part of the patient data collected to assess the patients pain score. These evaluations should be noted in the patient’s nursing notes and communicated to other team members to ensure continuity of care where pain management should be adjusted according to the patient’s response to the medication and taking their disease process into consideration (Monteiro et al. 2022).

Management in Kirby’s Rule of 2

physiological needs is a natural alert system that responds as a mechanism of protection of these needs. These responses are drowsiness, hunger, thirst, nausea, pain, and dyspnea. Most patients in an ECC setting are hospitalized because one or more of these needs are compromised (Hopper et al. 2015). Kirby’s rule of 20 further supports this concept with a ­similar narrative specific to the ECC veterinary setting. This list of 20  monitoring parameters that should be checked daily (or even more ­frequently depending on case severity) is considered the gold standard in regard to parameters to keep in check when caring for critical patients in the ICU (Table 9.2). This further supports the idea that high-­ quality nursing care, from frequent bed changes, spot-­cleaning cages (to reduce stress-­ inducing odors), to providing access to clean water, fresh food, padded comfortable bedding, and adequate pain management are all patient care fundamentals. More specifically, if a patient is in pain or uncomfortable, it is less likely to breathe efficiently (often panting or Table 9.2  Kirby’s rule of 20.

9.4  ­Nursing Care and the Role of Pain Management in Kirby’s Rule of 20

●● ●● ●● ●●

The importance of good nursing care cannot be overlooked in the veterinary ER or ICU. A large part of nursing care is the ability to observe and provide interventions when a patient’s needs change or aren’t being met. As a result, a foundational understanding of the fundamentals of basic physiological needs is required. This is easily demonstrated by Maslow’s original hierarchy of human needs which has been highlighted to demonstrate that the highest priority (foundational) needs are shared between humans and animals. These foundational needs are identified as ventilation, tissue integrity, toxin avoidance/ clearance, water balance, nutrient intake, and sleep. In contrast, the sub-­hierarchy of these

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●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●●

Body temperature Heart rate, contractility, rhythm Oxygenation and ventilation Blood pressure Fluid balance, colloidal osmotic pressure Mentation Nutrition Gastrointestinal motility and integrity Drug dosage and metabolism Pain control Wound care and bandages Immune status, antibiotics Glucose Renal function Electrolytes Red blood cells and hemoglobin Albumin Coagulation Nursing care Tender loving care

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patients who are not normally masticating. Additionally, patients who are sedated and very sensitive to sounds can be comforted by keeping them in a quiet area and placing ­cotton in their ears. While performing these hands-­on nursing techniques, the intention should come from a place of compassion and even love. As mentioned in Chapter  3, Section  3.7.8, social resilience is a newer ­perspective of improving patient outcomes. A  patient, animal, or human, when feeling supported and cared for leads to better and quicker positive outcomes.

9.5  ­Pain and the Physiological Stress Response: A Summary Figure 9.1  A patient with several broken ribs and severe trauma. This patient was breathing rapidly and shallowly before intercostal blocks were performed. After the intercostal blocks were performed the animals SpO2 and overall demeanor improved significantly. Source: Courtesy of Stephen Niño Cital.

hesitating to breathe comfortably) if they have visceral or thoracic pain. Likewise, the patient is less likely to eat, drink, or sleep if in discomfort or pain (Figure 9.1). Although much attention has been placed on pharmaceutical interventions to manage acute pain, patient comfort can contribute to the ultimate goal of patient well-­being and improved recovery. Patients that are recumbent should have pressure points well padded (elbows, hips) and their body position rotated on a regular schedule. This is also important during patient transport and diagnostic ­imaging. Padding should be used when a patient is placed in potentially uncomfortable positions in the magnetic resonance imaging (MRI), CT  scanner, or ultrasound table. Keeping the patient in a “physiologic” position (head elevated, sternal recumbency) should be attempted if possible. Severely ill patients may not blink normally and are at risk for corneal ulceration; artificial tear ointment should be applied often. Mouth care may be needed for

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The physiological stress response (PSR) or stress cascade encompasses any external or internal condition that challenges homeostasis. It is accompanied by neuroendocrine signaling that alters physiological and metabolic processes intended to cope with the homeostatic challenge. Painful conditions in the emergency setting are most often caused by a disruption of homeostasis by physical trauma or pathology from a disease process. Pain is linked to the PSR, whereby the PSR can intensify and exacerbate pain and vice versa (Gaynor and Muir  2009). This emphasizes that pain should be a treatment priority in patients admitted to the ER or ICU setting. Pain and stress are intimately related. The stress response typically begins with stimulation of the sympathetic nervous system and release of the sympathetic ­catecholamines epinephrine and ­norepinephrine. These increase heart rate, induce peripheral vasoconstriction, and divert blood to skeletal muscle and critical organs such as the heart and brain (Muir  2009). Additionally, the release of cortisol and glucagon cause insulin resistance, gluconeogenesis, and glycogenolysis leading to glucosemia and potentially glucosuria (Hurrle and Hsu 2017). Cortisol also functions as a glucocorticoid, suppressing the immune response to an insult, potentially paving the way for overwhelming infection. Vasopressin, sometimes called

9.6 ­Sleep Deprivatio

antidiuretic ­hormone (ADH), is released from the posterior pituitary and functions to increase water ­resorption in the kidney in response to hypovolemia. While cortisol produces immunosuppressive effects, inflammatory cytokines (such as  IL-­1, IL-­6, and tumor necrosis factor-­alpha [TNF-­α]) influence neutrophil migration, local vasodilation, and vascular permeability (Muir 2009). If produced in enough quantities and released systemically, these mediators can also induce dysbiosis and more seriously a systemic ­inflammatory response syndrome (SIRS) causing widespread vascular permeability and fluid imbalance, hypotension through various mechanisms, and hypercoagulability through activation of tissue ­factor expression on endothelium (Muir  2009). All of these deleterious effects result in mortality in critically ill patients. If left unchecked, this inappropriate overcompensated homeostatic mechanism can result in the death of a critically ill patient. Because pain and stress are interrelated, aggressive pain management strategies are essential in affecting the morbidity and mortality of veterinary patients in the ER (Figure 9.2).

There are many other factors within any veterinary situation that can contribute to an increase in a patient’s pain response. Anxiety has been shown to increase pain response in a variety of situations  – one such study in humans tested the effect of perioperative anxiety on postoperative pain and found such a definitive correlation that the location altered their perioperative counseling and postoperative pain protocols for patients with high ­anxiety (Kumar  2015). An estimated 70% of canine patients present to the veterinarian with anxiety, the correlation between anxiety and pain response becomes extremely significant to those in the veterinary field (Edwards et al. 2019). A similar percentage of cats, if not greater, also presents with anxiety. Patients who regularly exhibit anxiety when visiting the veterinary clinic can benefit greatly from previsit medications such as trazodone or gabapentin, and in return may need less pain medications during their visit (Kim et al. 2022). While previsit medications are not always recommended or feasible in the ER setting, their use once in the ER should be quickly assessed and given when appropriate (Gurney and Gower 2022). Additionally, low stress handling techniques can often decrease the incidence and/or intensity of anxiety, as proven by any number of studies.

9.6  ­Sleep Deprivation

Figure 9.2  This patient presented to the ER after being sent home the same day post thoracic limb amputation with only tramadol. The patient was in severe pain and was eventually euthanized after going into shock and producing bloody/brown urine which was suspected myoglobinuria secondary to rhabdomyolysis. Sending an animal home on only tramadol after a major surgery is both inappropriate medically and unethical. Source: Courtesy Stephen Niño Cital.

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Sleep deprivation is a common issue for veterinary patients who are hospitalized. Treatments are spread out around the clock  – vital sign checks, blood pressures, medication administrations, walks, or litter box cleanings are all common treatments occurring anywhere from every 2 hours to every 8 hours. The constant opening and closing of kennel doors, use of overhead lights, noise from staff or other patients, and interaction with veterinary staff can rob even calm veterinary patients of their regular sleep schedule. Sleep deprivation increases sensitivity to many pain stimuli, decreases the threshold of tolerance, and

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changes pain modulation after only 24 hours (Staffe et al. 2019). Patient treatments should be scheduled in such a way that they have the opportunity to rest and sleep to avoid contributing to any pain they may experience; ambient lighting should be reduced during nighttime hours to simulate a normal day/night cycle. Addi­tionally, sleep deprivation increases anxiety levels and can therefore create a doubly strong increase in pain response. Studies in human adults (Thille et  al.  2018), children, and mice (Zhang et al. 2023) all show a correlation between ICU delirium and the disruption of sleep cycles. The use of nocturnal dexmedetomidine in patients who are sleep deprived provides both pain control and sedation, allowing more comprehensive rest and ­recovery. In one study, ICU-­bound adults that received a dexmedetomidine CRI suffered less memory loss; in another, children given dexmedetomidine were observed to have improved REM sleep; in sleep-­deprived mice, hippocampal neuroinflammation was inhibited, promoting hippocampal neurogenesis.

9.7  ­Windup Pain in the ER Windup pain is commonly and inaccurately used interchangeably with the term central sensitization. It occurs with repeated activation of unmyelinated (c-­fiber) nociceptors, leading to a reduction in the activation threshold. This ultimately results in a progressive increase in intensity in the elicited response of dorsal horn neurons from repetitive c-­fiber activation. Although windup pain and central sensitization have close similarities, such as the activity at the NMDA/AMPA receptors, neurokinin receptors, and activation by C-­fibers, it should be noted that they are not the same (Mendell 2022). Windup is homosynaptic and more short-­lived in duration (usually occurring in less than a minute) and resolves quickly if the pain stimulus subsides. In contrast, central sensitization often occurs because of

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untreated windup pain or untreated chronic pain and is longer lived in duration. Central sensitization builds over time and degrades over a much longer period of time as well when compared to windup pain. Furthermore, central sensitization can occur without the occurrence of windup pain; for example, in cases of lifelong chronic and progressive pain-­ causing conditions such as Chiari-­like malformation. Central sensitization leads to allodynia (exaggerated and inappropriate response to nonpainful stimuli to noninjured tissue) and hyperalgesia (exaggerated response to lightly induced stimuli to injured tissue). A simple example of this is when a small cut is left untreated and results in pain throughout the entire digit or limb. When left untreated, ­neuroplastic changes can occur, resulting in  persistent pain, even after tissue healing has  occurred. The use of NMDA receptor antagonist medications, such as ketamine and amantadine, is a mainstay in the treatment of windup and central sensitization (Blanpied et al. 2005).

9.8  ­Techniques and Nuances for Analgesic Delivery in the Emergency Room A variety of techniques are available for managing acute pain. Typically, an initial bolus injection of a first-­line analgesic (preferably a pure agonist opioid) will have antinociceptive effects within 1–2 minutes depending on the agent used. Fentanyl is often used as a first-­ choice bolus injection for emergent patients presenting to the ER where pain exists from known, or more often, unknown causes (Gruen et al. 2022). Fentanyl is often preferred due to its short duration of action facilitating the ability to provide immediate and reversible analgesia while further case investigation and decision-­making can occur. This pain-­relieving effect helps facilitate a more thorough physical examination of the patient as well as additional procedures such as intravenous (IV)

9.8  ­Techniques and Nuances for Analgesic Delivery in the Emergency Room

catheter placement, phlebotomy, and diagnostics. Veterinary technicians should monitor the reaction to the medication being administered to help determine if the dosing was adequate or if the patient continues to experience pain. The findings should be discussed with the veterinarian, and additional medication or other approaches should be used if an inadequate therapeutic response is observed.

9.8.1  Pain Vacations (Acute Pain) Recent trends in both human and veterinary medicine utilize a technique for managing chronic pain patients by admitting them into the hospital for what is termed pain vacations. This technique is not well described in the ­literature, but the concept is to “reset” and restore more practical pain management techniques, such as oral therapies, by minimizing or stopping windup pain or mitigating central sensitization. Pain vacations should also be considered in the ER/ICU setting for patients experiencing severe and extreme pain that seems unresponsive to intermittent injectable analgesics or oral analgesics. Pain vacations require an IV catheter and a dedicated staff member to monitor the animal during the initial infusions and sedation. Ideally, the animal is sedated when safe. Sedation can be achieved by using a loading dosage of an opioid such as fentanyl, a benzodiazepine, micro dosages of dexmedetomidine, and most importantly, ketamine (Niesters et al. 2014). Because the NMDA and AMPA receptors have been recognized as a key component of the phenomenon of central sensitization, they are an important target when using this technique. The dosing and duration of a patient’s ketamine infusion can vary depending on the patient’s condition and response; in one human study, the mean total dosage per ketamine infusion was found to be 0.9 (+0.4) mg/kg, while another rated anything below 400 mg/human to be low-­dose ketamine; the infusions lasted anywhere from 30 minutes to 8 hours. Dosing in animals is still anecdotal but typically start with a 1–5 mg/kg

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loading dosage followed by a 0.5–1 mg/kg/hr CRI. Animals with heart disease should use lower or even micro-­dosages (0.1–0.5 mg/kg/hr) of ketamine to avoid the negative inotropic effects. An opioid of choice is usually added as  a CRI at lower dosages (e.g. fentanyl at 3–5 mcg/kg/hr), following a loading dosage. The addition of a lidocaine CRI in dogs is also worth consideration particularly for suspected visceral pain. Dexmedetomidine may also be considered. The difference between a pain vacation and a multi-­drug CRI, like a ­morphine/lidocaine/ketamine CRI commonly used in surgery for gas anesthetic reduction or in the postoperative period, is the intentional sedation and very slow recovery with the continued CRIs. In severe pain cases, during the sedation part of the pain vacation, local or regional nerve block techniques can also be performed.

9.8.2  Lidocaine Use in ECC With the ongoing shortages of opioids and in places where opioids are not available in any capacity, other options must be considered. ER IV infusions of lidocaine in canines can provide a valuable adjunct and, in some cases, an alternative to opioid analgesia when used with other analgesic medications such as ketamine and dexmedetomidine to control pain, especially in patients exhibiting abdominal pain (Lovell et  al.  2022). In critical surgical patients, multiple studies have shown a decrease in  inhalant requirements in dogs receiving a lidocaine infusion (Matsubara et al. 2009; Columbano et al. 2012). Previous as well as updated studies continue to support the hypothesis that lidocaine can also help to prevent reperfusion injury and reduce the risk of developing DIC or SIRS (Caracas et  al.  2009; Jiang et  al.  2020; Karnina et al. 2021). Furthermore, lidocaine has been shown to have anti-­inflammatory properties that can help with visceral and full-­body pain  (such as with burn patients) as well as prokinetic ­properties making it beneficial in

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preventing postoperative and opioid-­induced ileus (Yau  et  al.  2021). Lidocaine infusions should be used cautiously in cats and at much lower dosages than in dogs due to cats increased cardiovascular sensitivity to lidocaine. A low-­dosage lidocaine infusion should be considered in cats only when other attempts at managing pain have been shown to be ineffective.

9.8.3  Opioid Analgesia for Emergency and Critical Care Patients Opioids are discussed in detail in Chapter  5; however, some specific information related to the ECC setting is covered here. Morphine is an outstanding analgesic in dogs, but similar to other medications in felines, cats metabolize it differently than their canine counterparts. That is, cats eliminate morphine at a similar rate to dogs; however, they produce lower concentrations of morphine-­3-­glucuronide, and do not produce morphine-­6-­glucuronide (M6G), the active metabolite responsible for analgesia in human patients (Steagall et al. 2022). It is the metabolite of morphine, M6G, that binds with the mu receptor to produce an analgesic effect in humans and current research supports that morphine in cats, as a result, may be less effective in controlling pain than other available opioid options. Methadone is a opioid agonist with similar dosages and duration of action as morphine. Unlike the other opioid agonists, methadone is unlikely to produce vomiting or other undesirable GI effects. This makes methadone an outstanding preemptive ­analgesia in those ER patients for whom ­vomiting or abdominal contractions are ­contraindicated, such as those at high risk for  aspiration (laryngeal paralysis, brachycephalic syndrome) or those with gastric dilatation-­volvulus (GDV), abdominal pain, or an abdominal mass with a likelihood of producing hemorrhage. Methadone’s ­isomer is an antagonist at the NMDA receptor. Methadone’s unique pharmacology also shows

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contributions to the downregulation of  pain pathways by limiting the reabsorption of serotonin and noradrenaline, as well as obstructing the ­nicotinic cholinergic receptors. These actions elucidate the possible ­anti-­hyperalgesic impacts demonstrated by mechanical nociception (Bortolami and Love 2015). Remifentanil, sufentanil, and alfentanil are an ideal choice for ER patients who have experienced some sort of trauma with a neurological component and who require serial neurologic exams. Because they are ultrashort acting, the infusion can be discontinued and the exam performed 10–15 minutes later – with the assurance that any abnormal neurologic signs are not attributable to opioid-­induced sedation. Remifentanil also does not require hepatic metabolism, making it an ideal choice for patients where liver disease or shunts are suspected.

9.8.4  Local/Regional Analgesia in ECC Stopping pain at the source in a clinical setting should be done whenever possible. An in-­depth discussion on local regional pain management is covered in Chapter  6. Nonetheless, it should be noted that sentiments such as “these techniques take too much time” or “pain management will delay treatment” is false. With proper training, local regional blocks can be performed by a trained staff member expediently while other preparations for meeting patient needs are being performed. Examples of commonly seen emergencies that can benefit from stopping the pain that is either occurring or inflicted iatrogenically include felines with lower urinary tract ­blockages (especially those that are not safe to anesthetize), limb fractures, blunt thoracic trauma, lacerations, ocular proptosis, and ­surgical dystocia patients. In the ICU, nerve blocks, continuous infusions (soaker catheters, administration via chest tube), and subcutaneous infiltration of local anesthetic agents into

9.8  ­Techniques and Nuances for Analgesic Delivery in the Emergency Room

or around ­damaged tissue can provide rapid and short-or long-­term local anesthesia, depending on which agent is used. The minimum concentration of local anesthetic necessary to block conduction is higher for motor nerve fibers than for sensory fibers, so sensory anesthesia can occur without motor blockade. Administered locally, these drugs tend not to cause systemic side effects; however, the safe maximum dosage must be observed. Feline patients tend to be sensitive to local anesthetics (Campoy and Read  2013; Monteiro et  al.  2022), and proper dosing is important to minimize side effects.

9.8.5  NSAIDS Use of NSAIDs in the emergency patient can be beneficial; however, NSAIDS should be withheld until the patient is well hydrated, cardiovascular stability is improved, and adequate renal function has been confirmed. NSAIDs should also be withheld in patients where hemorrhage or other hemodynamic instability is present.

9.8.6  Maropitant Off-­label use of the drug maropitant (Cerenia®) for control of visceral pain in dogs and cats has been debated over the last 10 years. Several recent studies mention its use as an adjunct component to multimodal pain management for decreasing visceral pain, but the analgesic efficacy was not the primary study aim nor where the studies designed to assess its efficacy for pain (Corrêa et al. 2019; Corrêa et al. 2021). In addition to its antiemetic and possible ­anti-­nausea effects, which can exacerbate the  patient’s overall pain experience, there is ­evidence to suggest anti-­inflammatory (via ­inhibition of substance P) properties (Hay Kraus 2017; Tsukamoto et al. 2018). Some evidence supports that due to its NK-­1 receptor antagonism, it may be beneficial in neuropathic pain management, although much

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more research is needed for practical clinical implementation and confidence in stating maropitant should be used as an analgesic. At this point, it is fair to state that maropitant is continuing to show its usefulness as a ­complement to a multimodal analgesia. Maropitant should never be used as a sole agent for the purposes of analgesia until high-­ quality studies are performed.

9.8.7  Physical Rehabilitation Methods in ECC With the understanding that patients in ECC settings experience suffering when their physiologic needs are not met, it is important to also understand that nonpharmacologic interventions can contribute to improving patient comfort and healing. In recent years, more research is supporting the use of many physical rehabilitation modalities to improve patient outcomes in the critical care setting to help with reducing pain, inflammation, and edema in a variety of patients, particularly trauma and postoperative patients. The most commonly applicable modalities previously and currently used in the ECC setting include passive range of motion, massage therapy, and supported movement whenever possible (in primarily otherwise recumbent patients). Movement of patients is beneficial in improving GI motility, nutrient absorption, lung health, and reduction of edema due to improving circulation. In addition to these more commonly used modalities, the adjunct use of photobiomodulation (laser therapy), pulsed electromagnetic therapy, extracorporeal shockwave therapy, stem cell therapy, platelet-­rich fibrin therapy, and hyperbaric oxygen therapy are now being added. Many of these modalities are targeted at benefiting postoperative and trauma patients by helping reduce inflammation, improving tissue circulation, and reducing pain and inflammation (Bunch 2023). These modalities, their application, and their benefits are more extensively covered in Chapter 16.

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9.9  ­Common Painful Conditions in the ER/ICU Setting The veterinary caregiver, rather than asking whether a certain patient is in pain or not, should assume some degree of discomfort or pain in most patients that are critically ill or injured. Conditions not typically thought of as being painful, such as abdominal bleeding, have been described in humans as quite uncomfortable. As mentioned earlier in the chapter, when possible, objective analyses utilizing an appropriate pain scale is the best way to determine pain scores, rather than utilizing caregiver “assumptions.”

9.9.1  Fractures The presentation of animals that have suffered a bone fracture is not uncommon. Stabilization of the patient, which includes analgesics – typically with an opioid – should be started. After the patient is stable and comfortable, ­immobilizing the fracture site when feasible is highly encouraged. Immobilizing the fracture includes splinting, half casting, Robert Jones bandage technique, and modified Robert Jones technique to prevent further soft tissue trauma from displaced fractures and the pain associated with bone on bone rubbing at the fracture site (Figures 9.3–9.5).

Figure 9.3  Dogs with modified Robert Jones bandages applied. Source: Courtesy of Brian Goleman and Brian’s Bandages.

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Figure 9.4  Dogs with modified Robert Jones bandages applied. Source: Courtesy of Brian Goleman and Brian’s Bandages.

Figure 9.5  A dog that was sent home with a bandage that was not properly cared for or changed leading to soft tissue trauma and more discomfort. Source: Courtesy of Stephen Niño Cital.

9.9 ­Common Painful Conditions in the ER/ICU Settin

9.9.2  Acute Soft Tissue Injuries Acute soft tissue injuries (muscle strains/ sprains, full or partial cranial cruciate ligament rupture) occur frequently in active or overweight animals. These patients are usually treated pharmaceutically with an NSAID, acetaminophen, and possibly parenteral tramadol (oral tramadol in dogs is not recommended) and cage rest. They may also be given an injection of an opioid at presentation, depending on their discomfort level. Low-­level therapeutic lasers can also be ­considered. Thermal therapies, such as icing, have been proven effective for acute pain (Gruen et al. 2022).

9.9.3  Feline Lower Urinary Tract Obstruction This is likely one of the most common veterinary emergencies seen in general, emergency, and referral practice settings. With that in mind, these can be some of the most painful and unstable patients presenting in a triage situation. Due to the high propensity of fatally elevated potassium levels (resulting in cardiovascular instability), these patients must be treated immediately and are often not good anesthetic candidates in any ­capacity. The use of a caudal epidural or sacrococcygeal block along with an IV or IM opioid such as methadone can provide safe, effective, and expedient ­multimodal analgesia to these patients. Sacrococcygeal blocks can be safely and ­easily done by credentialed veterinary staff with lidocaine or bupivacaine (Steagall et al. 2017). This technique can also help with the placement of a urinary catheter while removing the obstruction as it relaxes the urethra and helps ­provide a smooth and comfortable recovery (See Chapter 6).

9.9.4  Trauma Patients Trauma patients are often the most easily ­recognized patients in need of acute pain ­intervention. Oftentimes on presentation a ­multitude of physiological processes are at

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Figure 9.6  A Yorkie experiencing evisceration after dog attack. The dog was given an opioid and placed under general anesthesia for flushing and bandaging before surgery. Source: Courtesy of Stephen Niño Cital.

play including neuroendocrine, immunological, and autonomic, sympathetic, and central nervous system responses. With these processes in  mind, choosing quick, and effective pain management can sometimes be challenging. Utilizing short-­acting drugs such as fentanyl (or sufentanil, alfentanil, and remifentanil) is not only cost-­effective, but also the simplest and most effective way to initiate pain management until it is determined that the patient is  hemodynamically stable enough for other pain  management interventions. A ketamine infusion can also be considered as beneficial in  trauma patients (Figure 9.6). Practitioners should not assume that a sick or injured patient not showing overt pain signs is not in pain.

9.9.5  Abdominal Pain in ECC Patients Abdominal pain patients with conditions such as pancreatitis or peritonitis are often in severe pain. These patients do best with

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Figure 9.7  A cat experiencing acute abdominal pain that was later diagnosed as severe triaditis.

­ ospitalization and concurrent infusions of h lidocaine, ­ketamine, and low-­dosages of an agonist opioids. A low-­dosage dexmedetomidine ­infusion can also be administered if the ­lidocaine and opioid alone are ineffective and the patient is hemodynamically stable. Interpleural blocks are beneficial in patients exhibiting cranial abdominal pain. Epidural morphine can also be used to relieve pain associated with pancreatitis and peritonitis (Robertson 2005). Owners can administer transmucosal or intra-­nasal buprenorphine at home if hospitalization is not an option. Application of transdermal buprenorphine (Zorbium®) in hospital will provide 96 hours of analgesia without the concern of dispensing a controlled drug. Gastrointestinal (GI) obstruction resulting from foreign body ingestion can produce intense, severe abdominal pain. Patients with GI obstruction often require emergency surgery to relieve the obstruction, reduce intestinal plication, and prevent or resolve intestinal intussusception. Aggressive pain management is crucial to ensure patient comfort and promote healing (Figure 9.7).

9.9.6  Acute Swelling and Edema Acute swelling and edema is often overlooked as a painful condition but can be quite

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Figure 9.8  A dog with moderate facial swelling secondary to a rattle snake bite. Source: Courtesy of Stephen Niño Cital.

­ ncomfortable as nerves are stretched and u compressed. In some cases, white blood cell migration and other inflammatory mediators are localized in higher densities in the swollen tissue that can sensitize nociceptors. When swollen secondarily to infection, severe inflammatory responses, insect bites/stings, or other venomous animal bites, tissue damage should be treated with the appropriate medications depending on its etiology (e.g. antihistamines, antidotes, etc.). Regardless, all animals with moderate to severe swelling deserve systemic analgesics to manage patient comfort. Therapeutic massage and icing may also be useful (Figure 9.8).

9.10  ­Conclusion Pain is the enemy of the ECC patient. Multiple studies in human and animal pain therapy demonstrate that pain control supports better mentation, comfort, and recovery. The options available are multitudinous and can frequently be combined in a multimodal model to affect various receptors and body systems to provide the best possible pain control for our patients.

 ­Reference

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69: 102733. https://doi.org/10.1016/j.amsu. 2021.102733. Kim, S., Borchardt, M.R., Lee, K. et al. (2022). Effects of trazodone on behavioral and physiological signs of stress in dogs during veterinary visits: a randomized double-­blind placebo-­controlled crossover clinical trial. Journal of the American Veterinary Medical Association 260 (8): 876883. https://avmajournals.avma.org/view/journals/ javma/260/8/javma.20.10.0547.xml. Kumar, S. (2015). Indian Journal of Health & Wellbeing 6 (6): 622–624. Lovell, S. et al. (2022). Randomized clinical trial comparing outcomes after fentanyl or ketamine-­dexmedetomidine analgesia in thoracolumbar spinal surgery in dogs. Journal of Veterinary Internal Medicine 36 (5): 1742–1751. https://doi.org/10.1111/jvim. 16514. Maíra, B. et al. (2021). Clinical validation of the short and long UNESP-­Botucatu scales for feline pain assessment. PeerJ 9 (e11225): 12. https://doi.org/10.7717/peerj.11225. Matsubara, L.M., Oliva, V.N., Gabas, D.T. et al. (2009). Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs. Veterinary Anaesthesia and Analgesia 36 (5): 407–413. Mellor, D.J. (2016). Updating animal welfare thinking: moving beyond the “five freedoms” towards “a life worth living”. Animals: An Open Access Journal from MDPI 6: 3–21. https://doi.org/10.3390/ani6030021. Mendell, L.M. (2022). The path to discovery of windup and central sensitization. Frontiers in Pain Research (Lausanne, Switzerland) 3: 833104. https://doi.org/10.3389/fpain. 2022.833104. Monteiro, B.P., Lascelles, B.D., Murrell, J. et al. (2022). 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain. Journal of Small Animal Practice 64 (4): 177–254. https://doi.org/10.1111/jsap. 13566.

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Muir, W. (2009). Pain and stress. In: Handbook of Veterinary Pain Management (ed. J.S. Gaynor and W. Muir), 42–56. St. Louis, MO: Mosby. Niesters, M., Martini, C., and Dahan, A. (2014). Ketamine risks and benefits. British Journal of Clinical Pharmacology 77: 357–367. https://doi.org/10.1111/bcp.12094. Robertson, S. (2005). Epidural injection and catheter placement. Clinician’s Brief (April): 53–57. Rousseau-­Blass, F. et al. (2020). Prevalence and management of pain in dogs in the emergency service of a veterinary teaching hospital. The Canadian Veterinary Journal 61 (3): 294–300. Simon, B.T., Scallan, E.M., Carroll, G., and Steagall, P.V. (2017). The lack of analgesic use (oligoanalgesia) in small animal practice. Journal of Small Animal Practice 58 (10): 543–554. https://doi.org/10.1111/jsap.12717. Staffe, A.T., Bech, M.W., Clemmensen, S.L.K. et al. (2019). Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation, and facilitates temporal summation of pain in healthy participants. PLoS One 14 (12): e0225849. https://doi. org/10.1371/journal.pone.0225849. Steagall, P.V.M., Simon, B.T., Teixeira Neto, F.J., and Luna, S.P.L. (2017 May). (2017) An update on drugs used for lumbosacral epidural anesthesia and analgesia in dogs. Frontiers in Veterinary Science 12 (4): 68. https://doi. org/10.3389/fvets.2017.00068. PMID: 28553642; PMCID: PMC5427076. Steagall, P.V., Robertson, S., Simon, B. et al. (2022). (2022) ISFM consensus guidelines on the management of acute pain in cats. Journal of Feline Medicine and Surgery 24 (1): 4–30. https://doi.org/10.1177/1098612X211066268. Thille, A.W., Reynaud, F., Marie, D. et al. (2018). Are sleep alterations the cause of ICU delirium? American Journal of Respiratory and Critical Care Medicine 198 (5): 692–693. Tsukamoto, A., Ohgoda, M., Haruki, N. et al. (2018). The anti-­inflammatory action of maropitant in a mouse model of

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Zhang, S., Zhang, Y., Zheng, Y. et al. (2023). Dexmedetomidine attenuates sleep deprivation-­induced inhibition of hippocampal neurogenesis via VEGF-­VEGFR2 signaling and inhibits neuroinflammation. Biomedicine & Pharmacotherapy 165, 2023: 115085. ISSN 0753-­3322, https://doi. org/10.1016/j.biopha.2023.115085.

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10 Chronic Pain Management for the Companion Animal Taly Reyes1, Jessica Birdwell1, and Stephen Niño Cital2,3,4 1

The College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA Howard Hughes Medical Institute at Stanford University, Stanford, California, USA 3 Remedy Veterinary Specialists, San Francisco, CA, USA 4 The Veterinary Anesthesia Nerds, LLC, Sheridan, WY, USA 2

10.1 ­Introduction Much of what is understood about maladaptive pain  – commonly referred to as “chronic pain”  – and its treatment in companion animals has been derived and adapted from human medicine. Human literature notes that victims with chronic pain experience a “terrible triad,” where a vicious cycle of pain, ­depression, and irritability ends in suffering, sleeplessness, and sadness (Koffel et al. 2016).

10.2 ­The Complexity of Chronic Pain Chronic pain is a condition of pain, either continuous or intermittent, that persists past the typical recovery period causing neurophysiological and psychological changes (Norkus et al. 2015). Historically, chronic pain was also defined as pain that lasts longer than 3 months, however given the subjectivity of this 90-­day “rule,” the use of this metric has fallen out of favor. Over the last 20 years, many advances have aided in the understanding of how highly

complex chronic pain is, yet the condition is still poorly understood. Common chronic pain conditions in humans stem from headaches, previous injury, neuropathy, osteoarthritis (OA), cancer pain, and backaches but can include many other ailments. Numerically, the prevalence of chronic pain in humans residing in America is estimated at 20%, or 1  in every 5 adults (Yong et al. 2022). Although the exact prevalence of chronic pain in companion ­animals is not known, the 2022 American Animal Hospital Association (AAHA) Pain Management Guidelines documented chronic pain as more abundant in companion animals, with an estimation reaching 40% in canines, and greater than 50% in felines, mostly associated with osteoarthritis (Gruen et  al.  2022). Similar to humans, the presence of untreated chronic pain in animals can impair the quality of life for both the pet and their owner leading to that “terrible triad” (Wiseman-­Orr et al. 2004: Wiseman-­Orr et al. 2006). Conditions that cause chronic pain in ­companion animals are poorly addressed pain (surgical or injury) (Figure 10.1), chronic infection, OA, cruciate ligament rupture(s), luxating patella(s), oncologic/malignant pain

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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(a)

(b)

Figure 10.1  (a, b). A dog with neoplasia on the ventral side at the base of the tail. The tail was then removed. This scenario is the “perfect storm” for creating neuropathic pain in the animal. This dog had a sacrococcygeal block placed before surgery, Nocita® during closure, and was started on an NSAID, pregabalin and amantadine. Source: Courtesy of Stephen Niño Cital.

(such as osteosarcoma – OSA), pancreatitis/triaditis, feline interstitial cystitis, Chiari malformation, inflammatory bowel disease, feline odontoclastic resorptive lesions, stomatitis, glaucoma, intervertebral disc disease (IVDD), otitis, phantom limb pain post limb amputation or declaw laminitis, among many other sources. Although chronic pain is often associated with an injury or may occur secondarily to a chronic health condition, it may also occur independently of tissue damage or past injuries. In humans, these instances without a known cause typically originate psychologically, such as psychogenic pain or somatic-­related disorders (American Psychiatric Association 2013). Disorders like these are not well recognized in companion animals, but one possible example would be feline hyperesthesia syndrome (Norkus et al. 2015). This rare and bizarre illness of cats manifests itself with brief but violent episodes of agitation, self-­mutilation, and

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rippling of the skin when touched. The exact cause for feline hyperesthesia syndrome, however, remains unknown at this time. Chronic pain’s complexity involves both sensory and emotional components. Emotionally, the perception of pain ­corresponds to stress/ anxiety, fear, fatigue, and aggression that ­intensifies the neural  ­mechanism of sensory transmission (Monteiro 2020). Pain can be cautiously classified according to its duration (acute or chronic), by its anatomic origin (somatic, visceral, or neuropathic) and by its severity (mild, moderate, severe, excruciating). Chronic pain results from a combination of inflammatory, neuropathic, and functional mechanisms. There are many variations of chronic pain that can be subdivided in one of the following groups (Monteiro et al. 2022): ●●

Inflammatory pain is often considered acute/adaptive pain. Prolonged duration of

10.4 ­Common Chronic Pain Conditions

●●

●●

tissue damage however, can cause the inflammatory pain to persist, resulting in pathological or maladaptive pain. Neuropathic pain originates from physical damage to the peripheral nervous system or central nervous system. Dysfunctional or functional pain is a state where there is no physical damage to the nervous system, but pain persists as a result of abnormal functioning of the central nervous system.

Pain as an experience is activated by a noxious stimulus triggering nociceptors on the skin, muscles, joints, and/or viscera producing an inflammatory response in the nervous system. Signals are transmitted to the dorsal horn of the spinal cord via A-­delta (primary afferent nociceptors specific to high-­threshold and acute pain) and C-­fibers (primary afferent nociceptors associated with high-­threshold and chronic pain). This transmission finally reaches the cerebral cortex, where the information is perceived and initiates the body’s need for response  – inflammatory or motor in action. During chronic pain states, persistent activation of the peripheral nociceptors cause hyperexcitability, resulting in peripheral sensitization. The continuous nociceptive input from the periphery to the dorsal horn of the spinal cord further contributes to the development of central sensitization. Consequences of this activity give rise to windup, a condition created by increased membrane excitability, synaptic strength, and decreased inhibitory mechanisms resulting in altered responses to pain. In addition, chronic pain may cause A-­beta fibers, which are  ­sensory nerve fibers with low-­ threshold and innocuous sensations, to generate and transmit pain signals to the dorsal horn  (Monteiro  2020). These neurobiological changes influence the way the patient experiences the noxious stimuli by either exaggerating or amplifying a response. Hyperalgesia reduces the threshold for pain and is defined as an exaggerated increase in pain provoked by a noxious stimulus (an overreaction to a painful stimulus). Allodynia is defined as pain

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provoked by non-­nociceptive stimulus (e.g. a pain response to a stimulus that does not typically cause pain, such as touch) (Dowdy 2020). In all cases, chronic pain remains difficult to treat and can significantly impair the patient’s and client’s quality of life. For this reason, early recognition and treatment is the best action for chronic pain. It is important to educate owners and the whole veterinary team in identifying as well as assessing pain for starting treatments and slowing the progression (Gruen et al. 2022).

10.3 ­Neuropathic Pain Neuropathic pain originates from physical damage or disease of the somatosensory system. It is maladaptive and involves changes in the peripheral nervous system, spinal cord, brainstem, and brain as impaired nerves fire spontaneously and develop hyper-­responsivity to inflammatory and normally innocuous ­stimuli. As a result of these changes, patients show clinical signs of hyperalgesia and allodynia. In veterinary medicine, neuropathic pain is underdiagnosed and not well understood because in humans the definition relies on the description of the pain obtained from the patient (e.g. burning, stabbing, tingling) (Monteiro et al. 2022).

10.4 ­Common Chronic Pain Conditions 10.4.1  Chronic Joint Pain-­Osteoarthritis (OA) There is an important difference in chronic joint disease between dogs and cats. OA in dogs is considered a developmental disease that results in abnormal mechanical function of the joint, causing inflammation of the tissues and is usually developed early in young dogs (Figure 10.2 and 10.3). Musculoskeletal pain in cats is usually a combination of OA pain and pain from nonsynovial joints. Therefore, the term degenerative joint disease (DJD) is more suitable. Contrary to dogs, DJD in cats is not related to developmental

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Figure 10.2  Maximus, in a sitting position, places his weight on his front right paw and not his left, notice the splayed toes. The left thoracic limb also shows signs of muscle atrophy from a previous shoulder injury after being kicked by a horse. This is an example of a subtle display of chronic pain secondary to injury. Source: Courtesy of Stephen Niño Cital.

disease. In cats, similar to OA in humans, DJD is an aged-­related disease. Although it can also affect young cats (Monteiro et al. 2022). Treatment typically consists of both pharmacologic and nonpharmacologic modalities. NSAIDs, when safe for the patient, are typically effective as a first line and solo therapy. The more recent release of antineural growth factor (NGF) drugs like bedinvetmab (Librela®) for dogs, and frunevetmab (Solensia®) for cats are quickly replacing chronic NSAID administration with once-­a-­month injection. There is some contention on whether long-­term use of NSAIDs with the new anti-­NGF drugs are safe based on human complications. At present, it is not recommended to continue NSAIDs longer than 3 weeks after starting the anti-­NGF products. As DJD or OA progresses, other therapies may need to be considered. The use of addition pharmaceuticals like amantadine, pregabalin, 本书版权归John Wiley & Sons Inc.所有

Figure 10.3  This dog suffers from severe carpal hyperflexion (carpal laxity) syndrome, which can predispose animals to osteoarthritis sooner, along with ligament degeneration. Treatment in young animals may include splinting and proper nutrition to surgery, like arthrodesis. For animals that are already mature, developmental correction is not always possible. If the animal is not receiving a surgical correction, custom braces and analgesics are used. Source: Courtesy of Stephen Niño Cital.

gabapentin, and polysulfated glycosaminoglycans (PSGAG) are commonly used. A more recent therapy that may prove effective in some animals that present in moderate to severe pain is subcutaneous injections of ketamine at a dosage of 0.5 to 1 mg/kg once a week to start. Dosages would then be adjusted based on the patient’s response. To support the psychological component of chronic pain drugs like amitriptyline and even tramadol can be considered. Nonpharmaceutical approaches include careful weight management, supplements like cannabinoids, and physical rehabilitation techniques. It is not uncommon and encouraged to try multiple pharmacologic and non-­ pharmacologic means to find what best suits the patient. There are several newer therapies available for OA, such as Librela® or Solensia®, ­that are given once a month Synovetin OA®,

10.4 ­Common Chronic Pain Conditions

which is an injectable medical device that lasts for an extended period of time, and the piprant class of NSAIDs with a different mechanism of action compared to COX-­inhibiting NSAIDs.

10.4.2 

Oncologic/Malignant Pain

Cancer pain is one of the most debilitating symptoms, affecting 43–63% of human patients in any stage of the disease and up to 90% of human patients in the advanced stage of the disease. Although the prevalence of cancer pain in dogs and cats is unknown, it is presumed to be just as high a percentage as cancer is the major cause of morbidity and mortality in these patients. A survey done in the UK involving small animal veterinarians revealed that 87% agree that cancer pain is underdiagnosed and 66% disagree that cancer pain is easy to treat. Cancer pain can be acute, chronic, or both and is multidimensional in nature. It can be somatic or visceral, and it involves inflammatory and neuropathic components (Monteiro et al. 2022). In comparison to OA, malignant pain (e.g. affecting bone, tissue, organs, metastasis, etc.) combined with discomfort secondary to its treatment regimen (e.g. chemotherapy, radiation therapy) are difficult to assess and develop effective interventions (Figure 10.4 and 10.5). Recent studies showed development of cancer specific metrology instruments for dogs and cats to assess their quality of life (described later in this chapter). Some of the inquiries included in these questionnaires are physical state, interaction with the owner, activity levels, pain level and owner concern for their pet’s health (Lascelles et  al.  2019). Determining whether a patient is ailed with cancer is pertinent. Prolonging diagnosis or recognition can amplify chronic pain conditions secondary to the malignancy. Treatment of cancer-­related pain is extremely broad but generally consists of ­multimodal techniques used in both acute and chronic pain patients. Certain types of cancer-­related pain can be alleviated by therapeutic or palliative radiation and infusions of bisphosphonates that help prevent the loss of bone mass. 本书版权归John Wiley & Sons Inc.所有

Figure 10.4  A cat with advanced mandibular neoplasia. Source: Courtesy of Stephen Niño Cital.

Figure 10.5  Diego had an osteosarcoma on the left humerus. His pain was treated with carprofen, acetaminophen, gabapentin, and cannabis. Source: Courtesy of Stephen Niño Cital.

10.4.3  Chiari Malformation Pain Chiari-­like malformation is a congenital condition marked by an alteration in the shape and ultimate congestion of the brain and ­cranial cervical spinal cord. These changes can obstruct the flow of cerebrospinal fluid, leading to discomfort and potentially giving rise to fluid-­filled pockets in the spinal cord known as syringomyelia. The

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fluid within these pockets, or syrinxes, is similar in composition to CSF. Over time, these pockets might enlarge, damaging the spinal cord, which can manifest as pain and neurological impairments. The detection of Chiari-­like malformation related pain and syringomyelia has been on the rise, because of the increasing prevalence of pre­disposed brachycephalic breeds and the widespread use of MRI technology. Treatment of the ­associated pain can be very challenging. While surgery is often successful in humans, we do not have the same level of success in ­veterinary species at this time. There are many symptoms related to Chiari-­like ­malformation and syringomyelia, with the most reported including random yelping/­vocalization, spinal pain, activity change, anxiousness, aggression,

CM-P

SM-associated phantom scratching

NSAIDs

Gabapentin

Continuing pain

Continuing phantom scratching

Add/switch to gabapentin

sleep disruption, head aversion, grimace, repetitive barking, squinting/photophobia, and phantom scratching (Rusbridge  2020). Symptoms may become more frequent or worse during weather change or changes in barometric pressure. Attempts to study this affect in dogs have failed, but human anecdotes show a strong correlation between weather or ­barometric change and worsening of symptoms. Integrative techniques, such as adding 1–5 mg/kg melatonin PO twice a day and a full spectrum cannabidiol (CBD) product (VetCS Advanced Joint Formula with Cannabidolic acid (CBDA):CBD: Cannabigerol (CBG): cannabinol (CBN)) at 2 mg/kg PO twice a day, in combination with conventional pharmaceuticals have proven to be highly successful (Figure 10.6).

SM-associated gait abnormalities (weakness and postural deficits)

Physiotherapy/ hydrotherapy Consider referral/ surgical management

Pregabalin (switch from gabapentin)

Continuing pain

Continuing gait abnormalities

Continuing phantom scratching

Pregabalin (switch from gabapentin)

(Possible) CSF-reducing drugs • Cimetidine • Omeprazole • Acetazolamide

Corticosteroids (considered last resort)

Referral for more medical options and/or surgical management

Continuing pain

Alter polypharmacy/ add additional drug (aim for as few drugs as possible)

(Possible) CSF-reducing drugs • Cimetidine • Omeprazole • Acetazolamide

Amantadine or memantidine

Topiramate

Complementary therapy (eg, acupuncture)

Amitriptyline Cannabinoids (CBD oil)

Paracetamol For ‘top up’ medication during breakthrough pain

Figure 10.6  Chiari (CM-­P) and syringomyelia (SM) pain symptom flow chart. Source: Rusbridge, C. 2020 / with permission of John Wiley & Sons. 本书版权归John Wiley & Sons Inc.所有

10.4 ­Common Chronic Pain Conditions

packs to the head may also be beneficial (Vuralli et al. 2019; Tardiolo et al. 2019).

10.4.4  Headaches and Migraines in Animals Migraine in humans is defined as a recurrent headache disorder manifesting in attacks lasting 4–72 hours. (Plessas et al. 2013) There does not appear to be any reason why animals could not experience a headache or migraine ­disorder and likely are experiencing them. Symptoms of a headache or migraine, just like in humans, can be subtle to extreme. Reports in veterinary literature are scarce with possible symptoms that include ­behavior changes, ­isolation, aggression, hypersalivation, hyperesthesia, photophobia, lip smacking, ataxia, among ­several others. Treatment options include acetaminophen +/− codeine or hydrocodone, pregabalin, or gabapentin, cannabinoids, topiramate, and possibly micro dosages of dexmedetomidine. Acupuncture and cool ice (a)

10.4.5 Meningitis Meningitis is inflammation of the meninges from either infectious or noninfectious causes. Treatment of the underlying condition, which can be severe, is ­critical to getting the generalized pain under control. Since the meninges encapsulate the brain and spinal cord these animals are particularly susceptible to chronic pain that can be difficult to treat even after the primary cause has been treated. Prednisone is often used to decrease the meningeal inflammation. Other medications such as amantadine, acetaminophen, pregabalin, and gabapentin can also be used. Subcutaneous ketamine can also be used (Figure 10.7).

(b)

(c)

Figure 10.7  (a) Precious presented for severe generalized pain. A central spinal fluid tap concluded meningitis and she was started on prednisone and gabapentin. This was not successful in alleviating her pain and she was given 1 mg/kg of ketamine SC and sent home with amantadine. (b) After a few days of treatment for meningitis and on the new analgesics, she presented in a much more comfortable state. (c) While her meningitis has cleared, she is still suffering from chronic pain that is being managed with gabapentin and amantadine. Source: Courtesy of Stephen Niño Cital. 本书版权归John Wiley & Sons Inc.所有

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10.4.6  Chronic Wounds Chronic wounds are wounds that do not heal in the typical fashion, or a predictable period of time. Again, the subjectively defined three-­ month time frame for a wound to be considered “chronic,” is not dissimilar to that of “chronic pain” and should be considered on a patient to patient basis. While not all wounds meet this (a)

(b)

(c)

(d)

three-­month time period managing wounds for longer than a month can feel exhausting and stressful to the animal and its caretakers (Figure 10.8). Decubitus ulcers are a good example of chronic wounds that need constant attention and pain control (Figure  10.9). Typically, this may include frequent bandage changes, topical medications that can  include local

Figure 10.8  (a–d) This dog had severe decubitus ulcers that went down to the bone. The dog had reparative surgery when first presenting that failed due to the high movement and tension area over the elbow. The ulcers were then allowed to heal over 8 weeks by second intention. The dog came in initially twice a week for bandage changes, then once a week until completely healed. The dog was placed on a NSAID throughout treatment. Source: Courtesy of Stephen Niño Cital. 本书版权归John Wiley & Sons Inc.所有

10.7 ­Pharmacological Interventions

help guide appropriate treatment (Mathews et al. 2014; Today’s Veterinary Practice 2013)

10.6 ­Goals and Modalities for Treating Chronic Pain

Figure 10.9  This dog has been experiencing chronic pain due to a chain collar imbedded into its soft tissue. Source: Courtesy of Stephen Niño Cital.

anesthetics, and a systemic analgesic like an NSAID combined with regular assessments by a veterinary medical professional.

10.5 ­Assessing Chronic Pain Chronic pain can be more challenging to identify in comparison to acute pain. Chronic pain often has a slow progression resulting in gradual behavioral changes, which usually goes unnoticed by owners. Chronic pain can also be cyclical, where one day the animal seems comfortable, followed by the next day where the animal seems very uncomfortable (Monteiro 2020). For instance, a friendly 13-­year-­old cat acutely starts hissing when being pet by an owner could be a sign of chronic pain secondary to osteoarthritis. There are different ­objective and subjective measurements that aid in analyzing or monitoring this patient for  chronic pain described in Chapter  4. Implementing one to two of these pain assessments allows practitioners to more formally “grade” a patient’s pain state and therefore 本书版权归John Wiley & Sons Inc.所有

The main goals of chronic pain management in the companion animal include improving patient comfort, reducing the pain or noxious stimuli to the pain pathway, and overall better quality of life. Dealing with chronic pain can be a challenging, frustrating, and time-­consuming process for both the veterinary personnel and the owner. An individualized plan should be centered around the patient’s and client’s needs. Educating the owner on signs of pain/ discomfort in their pet, the disease processes occurring, as well as giving realistic expectations of duration, outcomes, and financial capabilities should be included during plan development. Although tempting, assuming a single medication will be effective long term is unrealistic given chronic pain’s complexity. The human and veterinary literature document best success in treatment when applying a triple approach that combines multimodal pharmaceuticals aids, lifestyle changes, and adjunctive therapies. An excellent example of this “triple approach” can be seen with elderly dogs experiencing OA. The first prong might include pharmacological agents such as nonsteroidal anti-­inflammatory drugs (NSAIDS), tricyclic antidepressants (TCAs like amitriptyline), and neuropathic pain relievers (e.g. gabapentin, amantadine). Second, lifestyle is addressed including an effective weight loss program, nutritional support, and regular low-­ intensity exercise. Finally, adjunctive therapies like therapeutic dosages of fish oil, low-­level laser, and cannabinoids may be added.

10.7 ­Pharmacological Interventions Many of the drugs effective for acute pain may have little or no benefit on chronic pain when used alone (Greene  2010). Fortunately, the

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pharmaceutical toolbox continues to grow and improve for our companion animals (Gruen et  al.  2022). Readers are advised to refer to Chapter  5 for further detailed discussion on individual agent pharmacology. The common drug classes listed below describe some of the nuances of using these drugs in the chronic pain patient.

10.7.1  Pain Vacation (Chronic Pain) Pain vacations for chronic pain patients are used when at home therapies become seemingly ineffective, or over exertion of a chronic pain patient occurs. An example of overexertion would be the patient feels reasonably well one day and plays too long and too hard and is unable to ambulate later that day or the next day with minimal relief from their chronic pain medications. Although not well described in the literature, the concept is to “reset” and restore more practical pain management techniques, such as oral therapies, by minimizing or stopping windup pain or mitigating central sensitization. Pain vacations require an IV catheter and a dedicated staff member to monitor the animal during the initial infusions and sedation. Ideally, the animal is sedated. Sedation can be achieved by using a loading dosage of an opioid such as fentanyl, a benzodiazepine, micro dosages of dexmedetomidine, and most ­importantly, ketamine. Because the N-­methyl-­ D-­aspartate (NMDA) and α-­amino-­3-­hydroxy­5-­methyl-­4-­isoxazolepropionic acid receptor (AMPA) receptors have been recognized as a key component of the phenomenon of central sensitization, they are an important target when using this technique (Madden et al. 2011). The dosage and duration of a patient’s ketamine infusion can vary, depending on the patient’s condition and response. Dosing of ketamine for this technique in animals is still anecdotal but typically starts with a 1–5 mg/kg loading dosage followed by a 0.5–1 mg/kg/h. CRI. Animals with heart disease should use lower or even micro-­dosages (0.1–0.5 mg/kg/h) of ketamine

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to avoid the negative inotropic effects of ketamine. An opioid of choice is usually added as a CRI at lower dosages (e.g. fentanyl at 3–5 mcg/ kg/h), following a loading dosage. The addition of a lidocaine CRI in dogs is also worth consideration, particularly for suspected visceral pain. Dexmedetomidine may also be considered. The difference between a pain vacation and a multidrug CRI, like a morphine/lidocaine/ketamine CRI commonly used in surgery for gas anesthetic reduction or in the postoperative period, is the intentional sedation and very slow recovery with the continued CRIs. The infusion period is anywhere from 2 to 6 hours. In a human study, chronic pain sufferers in each study reported a dramatic decrease in pain levels that lasted anywhere from 3 weeks to 4 months (Patil and Anitescu  2012; Orhurhu et al. 2019).

10.7.2 Mesotherapy Mesotherapy is the technique of injecting various analgesics intradermally or subcutaneously around a painful joint. Its practice is relatively new in animals with only minimal support in the literature. Alves et al. (2022), in a prospective, randomized, double-­blinded study, 30 working dogs suffering from hip osteoarthritis were included as participants. These dogs were randomly divided into two groups: the treatment group, which received mesotherapy, and the control group, which was administered meloxicam orally. The mesotherapy treatment involved multiple intradermal injections around the hip joint, containing a combination of lidocaine, piroxicam, and thiocolchicoside. These injections were given on days 0, 7, 14, 21, 35, 49, and 63. The control group, on the other hand, received oral meloxicam for a duration of 70 days. The dogs’ response to treatment was evaluated through various clinical measurement tools, such as the Canine Brief Pain Inventory, Liverpool Osteoarthritis in Dogs, and Canine Orthopedic Index. These assessments were conducted by

10.7 ­Pharmacological Interventions

each dog’s trainer before treatment (T0) and at intervals of 15, 30, 60, and 90 days after treatment initiation. Results showed that dogs in the mesotherapy group exhibited significantly improved scores in pain severity, pain interference, and function, in comparison to the control group, at all post-­treatment time points. This suggests that mesotherapy effectively reduced pain severity, minimized the impact of pain on daily activities, and enhanced overall function in comparison to meloxicam treatment. Specifically, mesotherapy led to significantly improved gait scores compared to the control group on day 30. No significant adverse effects were observed in either group, except for one dog in the mesotherapy group experiencing vomiting. Mesotherapy emerged as a simple, minimally invasive, cost-­effective, and low-­risk treatment option for reducing pain levels and enhancing clinical scores in police working dogs with bilateral hip osteoarthritis. Mesotherapy involves injecting small volumes (0.1 ml) of pharmaceuticals intradermally using 4-­mm, 27-­gauge needles. These injections should be spaced approximately 2 cm apart and targeted over the specific area of concern. Proper cleansing of the hair and skin before administering the injections is recommended. This procedure can be carried out by general clinicians, typically without the need for sedation (Alves et al. 2022). The medications employed in mesotherapy may consist of a combination of a local anesthetic, a non-­steroidal anti-­inflammatory drug (NSAID) or corticosteroid, and a muscle relaxant. The microdeposits of these medications enable slow release into the underlying tissue, ensuring rapid onset of action and prolonged local effectiveness. The choice of specific medications may vary based on drug availability and individual patient requirements. While adverse effects associated with mesotherapy are rare, they may include nausea, diarrhea, mild pain, edema, pruritus, and

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erythema. It is advisable to monitor dogs for these effects following treatment.

10.7.3  Transdermal Medications Potentially safe and efficacious topical therapies include the use of transdermal patches (lidocaine, fentanyl, and buprenorphine). These agents operate using a sustained release delivery system to provide reduced drug ­accumulations, theoretically minimal fluctuations in plasma concentrations, prolonged drug responses, and less negative side effects (Steagall  2015). Historically, these topical agents have been used in dogs and cats to fight a variety of pain types, yet acute pain has been the primary focus. It is crucial that veterinary personnel and owners are aware of the high likelihood for ingestion by the patient, other household animals, or owners (more specifically children) when using topical agents. This could cause fatal adverse effects; therefore, all topical agents should be thoroughly investigated before application with the pros outweighing the cons for usage. It is not advised to use opioid containing patches as a first and only line of analgesia. Fentanyl patches are labeled for human use but are commonly used extra-­label in veterinary patients. They provide analgesia for moderate to severe pain associated with major surgical procedures or for chronic pain, particularly in the palliative care setting. Data is mixed on efficacy when used alone but when used as part of a multimodal approach could be just what a patient needs to stay comfortable. Lidocaine patches are another interesting option that have pharmacokinetic studies in animals, however, efficacy studies for pain are lacking (Steagall 2015). In humans a lidocaine patch applied over a painful area on a limb improves motor function resulting from reduction of pain without interfering with ambulation and is helpful in treating neuropathic pain secondary to shingles. This would suggest in order for the lidocaine patches to be useful in

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Figure 10.10  A potentially useful approach was to apply lidocaine patches. If nothing else, the patches will keep the incision site clean. Source: Courtesy of Stephen Niño Cital

animals, they must be applied close to the site of pain, which may not be always possible in our patient populations due to the risk of ingestion (Figure  10.10). They should also be used as an adjunct with other analgesics. More studies are needed for a thorough comprehension of their use. Zorbium is a long-­acting transdermal buprenorphine solution 20 mg/ml label to use only on cats 4 months or older. It provides analgesia associated with postoperative pain of elective surgical procedures but could be used for chronic pain, particularly in animals where pain is uncontrolled or palliative situations.

10.7.4  Non-­steroidal Anti-­Inflammatory Drugs (NSAIDs) With precautions, NSAIDs are a fairly safe class of drugs with a low-­risk-­to-­high-­benefit ratio that can improve the quality of life.

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Although adverse effects from NSAIDs ­administered are actually quite low, routine hematological and biochemical analysis is recommended for patients on long-­term NSAID therapy to analyze their effects on kidneys, liver, as well as intestinal tract. Several NSAIDs are available on the market today for treating chronic pain in canines. Long-­term use of NSAIDs have been studied showing an increased efficacy without ­augmenting organ-­based toxicity (Innes et al. 2010) and reported adverse events such as emesis, lethargy, or death were less with the non-­coxib NSAIDs when compared to the coxib NSAIDs (Hunt et al. 2015). In felines, there are fewer NSAID options labeled for long-­term analgesic support that is specific to musculoskeletal pain. The two main agents used are meloxicam and robenacoxib (Onsior™). With meloxicam’s diverse formulations available (injectable, oral, transmucosal gel, tablet) opportunities for varied routes are possible, although typically in small animals PO or injectable is preferred. Historically, meloxicam at 0.025 mg–0.05 mg/kg PO every 24 hours was used off-­label in cats by many veterinarians who felt this practice was safe; however, in October 2010, the Food and Drug Administration (FDA) announced the addition of a black box warning that read “repeated use of meloxicam in cats has been associated with acute renal failure and death” and strongly advised against this practice. Specifics on their recommendations for this and other NSAID use can be found at (https://animaldrugsatfda. fda.gov – NSAID labels. Subsequently, the long-­ term administration of NSAIDs to cats  has decreased in popularity in the USA. However, in the UK it is regularly administered with a label maintenance dosage of 0.05 mg/kg without reported incidence of adverse effects. Several studies have shown long-­term meloxicam dosage of 0.02 mg/kg can be safely given to cats, even those with chronic kidney disease (CKD) and greater than 7 years if otherwise clinically stable (Gowan et  al.  2011). In

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addition, a study in cats with CKD and DJD may have a slower progression of renal disease when given the long-­term meloxicam therapy (Gowan et al. 2012). Similarly, robenacoxib has significantly decreased owner-­assessed disability, increased activity by >10%, and improved temperament, and happiness after 6 weeks of treatment in a published study by Adrian et  al. (2021). Robenacoxib has been approved for repeated doses in both cats and dogs. The recommended extra-­label dosage used for cats with osteoarthritis is 1–2 mg/kg PO every 24 hours for up to 28 days (Jordan and Ray 2012). Other NSAIDs are documented in the literature for systemic use in cats but not all are licensed in all regions. It is important for veterinary teams to select an NSAID that fits their clientele and patients’ needs/response. For animals that are on daily NSAIDs, there has been some discussion suggesting every-­ other-­day administration and using the lowest effective dosage if there are renal or liver ­concerns, although overall efficacy may be impacted.

10.7.5  Acetaminophen Acetaminophen (also known as paracetamol) is a commonly used analgesic and antipyretic medication primarily used in humans. Although the exact mechanism of action of these drugs is not elucidated currently, it is believed to involve the inhibition of cyclooxygenase (COX) isoform COX-­3, a splice variant of COX-­1, and via activation of the descending serotonergic pathways to produce analgesia centrally (Monitto et  al.  2017). In canines, acetaminophen has been used at 5–15 mg/kg every 8–12 hours PO often combined in a fixed-­ dose product with hydrocodone at 0.22–0.5 mg/kg PO every 8 hours (not to exceed 15 mg/ kg PO every 8 hours. acetaminophen) or codeine 1–2 mg/kg PO every 6–8 hours (not to exceed 15 mg/kg PO every 8 hour acetaminophen) (Kukanich and Spade  2012).

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Anecdotally, acetaminophen seems most useful in dogs, either for short-­term use following surgery (acute pain), during the “washout period” when changing from one NSAID to another, or for short-­term pulse therapy in chronic pain states. In the majority of dogs, acetaminophen is well tolerated, although toxicity resulting in methemoglobinemia has been documented. Clients should give the medication exactly as directed by their veterinarian. Acetaminophen can be used with NSAIDs. Acetaminophen-­containing products should never be administered to cats since they are relatively deficient in activity of the enzyme glucuronyl transferase, which conjugates acetaminophen to glucuronic acid for excretion. This results in a manifestation of toxicosis with severe methemoglobinemia leading to hemolysis and death.

10.7.6 Corticosteroids There is often a love–hate relationship with corticosteroids for veterinarians, owners, and their patients. Corticosteroids act as ­anti-­inflammatory agents by blocking prostaglandins and leukotrienes. They inhibit prostaglandins at the level of phospholipase A2, which results in blockage of the COX pathway similar to NSAIDS. Corticosteroids are sometimes selected in cases as an adjunct for chronic pain management where profound anti-­ inflammatory effects can be beneficial; nevertheless, they are not without potential side effects. Long-­term corticosteroid administration can lead to panting, polyuria, ­polyphagia, polydipsia, behavioral changes, immunosuppression, increased risk of infection, decreased wound healing, gastrointestinal upset or ulceration, muscle and bone weakening, protein catabolism, iatrogenic Cushing’s disease, predisposition to diabetes, alopecia, chemotherapy treatment interference, and laminitis. Corticosteroids should never be administered simultaneously with NSAIDS or other corticosteroids because of a profound risk of

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gastrointestinal side effects including ulceration, GI perforation, and potentially sepsis or death. For example, a cat with ulcerated oral neoplasia in which owners select only palliative care may benefit from treatment with corticosteroids. Agents that are selected most commonly include tablet or liquid prednisone or prednisolone (in cats). Long-­duration injectable agents (e.g. Depo-­Medrol) are used less frequently due to their sustained and irreversible effects.

10.7.7 Opioids While opioids remain the mainstay treatment modality for many types of pain, they may not be as efficacious or practical in treating chronic pain. Considerable debate surrounds opioid use in the human chronic pain management field over issues such as effectiveness, concerns for opioid tolerance, opioid dependence or abuse, and opioid-­induced hyperalgesia (OIH). OIH is a reported condition in humans where patients taking long-­term opioids develop an increased sensitivity to pain, which has been seen and documented in companion animal literature as well. Veterinarians who prescribe oral opioids need to consider these issues along with the poor bioavailability, adverse side effects, and their efficacy in treating their patient’s chronic pain.

10.7.8  Atypical Opioids: Tramadol and Tapentadol Starting in the early to mid-­2000s, tramadol became popular among veterinarians searching for oral non-­NSAID options to treat acute and chronic pain in companion animals. Tramadol was attractive because the drug was  new and not controlled by the Drug Enforcement Agency. Despite the drug’s widespread use since then, its exact mechanism of action, clinical efficacy, human abuse potential, and potential side effects have at times

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brought the drug’s use into question. Many veterinary anesthesiologists prefer not to use tramadol in dogs as a first and only line of analgesic. It should always be paired with another analgesic such as an NSAID. In humans, tramadol has a weak mu agonist opioid property that inhibits serotonin reuptake (SSRI) as well as the reuptake of norepinephrine. Collectively, these actions along with the ability to antagonize N-­methyl-­d-­aspartate (NMDA) and agonize TRPV1 act centrally and appear to provide some level of analgesia-­though variable. As a result, it is widely used to treat moderate -­to-­severe chronic pain states in humans or other species. Due to both tramadol and tapentadol’s central action as a nontraditional opioid, they are assumed to be good adjuncts in the treatment of chronic pain in companion animals. Based on the literature, dogs appear to obtain some analgesia from tramadol through nonopioid mechanisms by producing the inactive metabolite N-­desmethyltramadol, while cats display improved antinociceptive effect due to rapid active O-­desmethyltramadol metabolite production with a prolonged half-­ life (Dominquez-­Oliva et al. 2021). In dogs, the potential analgesic dosage ranges from 4 to 10 mg/kg PO every 8 hours, with data suggesting ideally every 6 hours concurrently with other pharmaceuticals for best results (Guedes et  al.  2018). In cats, the analgesic dosage is 1–2 mg/kg PO every 12 hours with possibility for 4 mg/kg every 24 hours for breakthrough or severe pain. However, research notes that dosages greater than 2 mg/kg PO every 12 hours in geriatric cats can cause adverse effects that are neurologic and opioid overdose like in nature regardless of their ability to increase the level of activity and quality of life (Dominguez-­ Oliva et al. 2021). Along with the poor palatability, research suggests tramadol has a marked decline in oral bioavailability when administered for longer than one week specifically in dogs, suggesting it is a poor choice for use in the ongoing treatment for chronic pain. Tramadol is more

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commonly associated with negative side effects including but are not limited to the following: excessive panting, vocalization, restlessness, dysphoria, euphoria, sedation, hyporexia, diarrhea, mydriasis, depression, hypersalivation, and vomiting, etc. The exact etiology of these symptoms is not clear but is speculated to result from varying degrees of serotonin syndrome. Therefore, tramadol’s effects on serotonin should be weighed carefully when the drug is prescribed for use with other drugs that increase serotonin (e.g. SSRIs, TCAs, monoamine oxidase inhibitors), and its practice should be avoided or done only under very careful monitoring. Tramadol is also marketed with acetaminophen under the trade name Ultracet®. Tapentadol is considered a “second-­ generation” tramadol that is believed to work via a similar mechanism of action but has dual action (i) mu opioid agonism, (ii) with an inhibitory action on norepinephrine reuptake (Dominguez-­Oliva et  al.  2021). With an analgesic potency similar to morphine, it blocks modulation and perception of the nociceptive pathway via action on the mu opioid receptors of the ascending tracts with a higher affinity than tramadol (Dominguez-­Oliva et al. 2021). For veterinary patients, this may possess a more superior analgesic profile than tramadol. Other advantages include minimal dependence on metabolic activation in the liver, variabilities in genetic polymorphism that do not affect the patient response, as well as the lack of stimulation of the serotonergic pathways, reducing the overall probabilities for adverse reactions. Unfortunately, with higher costs and controlled drug handling protocols for tapentadol, it is unlikely to replace tramadol in companion animals long-­term. At this time the only documented dosages for companion ­animals were given by Gaynor and Muir ranging 5–10 mg/kg every 8–12 hours in  canines (Dominguez-­Oliva et al. 2021). More research is needed to fully understand its side effects, efficacy long-­term, and ideal dosage regimens.

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10.7.9  Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs) Numerous drugs that were initially developed in 1959 for people as antidepressants have become effective as adjunctive therapies for various conditions in human medicine. This includes but is not limited to migraine prophylaxis, OCD, insomnia, anxiety, and chronic pain. For chronic pain this class of drug appears to be most effective for conditions that are neuropathic in nature secondary to myofascial pain, diabetic neuropathies, fibromyalgia, and postherpetic neuralgia. These drugs predominantly work by their action on five ­different neurotransmitter pathways to block serotonin and norepinephrine reuptake. They also are competitive antagonists on postsynaptic alpha cholinergic, muscarinic, and histaminergic receptors (Moraczewski et al. 2022). Neurotransmitters are believed to play a role in the modulation of pain within the central nervous system (CNS) and may additionally have anti-­inflammatory effects on microglia (Obuchowicz et al. 2006; Tai et al. 2009). Since chronic pain states can be psychologically and emotionally draining (in humans). These agents have the added benefit of potentially improving mood, reducing depression, and reducing anxiety in companion animals with chronic pain. Amitriptyline, a widely prescribed TCA, acts to reduce serotonin and norepinephrine reuptake postsynaptically and therefore results in higher neurotransmitter levels. It is likely that amitriptyline also exerts analgesic effects through numerous other mechanisms including sodium, calcium, and potassium channels, neurotrophic tyrosine kinase receptors, and potentially NMDA receptors. Adverse effects include altered thyroid levels, sedation, constipation, hyperexcitability, dysrhythmias, bone marrow suppression, hyperglycemia, hyponatremia, vomiting, etc. Caution should be used when administering

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concomitantly with other pharmaceuticals that would worsen the risk of adverse effects. Amitriptyline dosage is typically 1–2 mg/kg PO every 12 hours with some documentation of up to 3–4 mg/kg in canines (Norkus et al. 2015). In cats for neuropathic pain, the dosage regimen is 0.5–2 mg/kg PO every 24 hours (Jordan and Ray  2012). Patients should be monitored with bloodwork, urinalysis, and electrocardiogram pre, intra and post therapy. Duloxetine is a serotonin–norepinephrine reuptake inhibitor (SNRI) that is effective for depressive and anxiety disorders in humans. In people, the drug has shown benefits in treating chronic pain states such as diabetic peripheral neuropathy, fibromyalgia, interstitial cystitis, musculoskeletal pain, anxiety, cognitive impairment, and likely several more. At this time, the use of duloxetine in companion animals is minimal, but further clinical experience with the drug is likely to be forthcoming in the next few years. Veterinary personnel should be advised that when using psychotropic agents concurrently that drug interactions can increase serotonin to debilitating levels resulting in a condition known as serotonin syndrome. In dogs, serotonin syndrome can cause agitation, dysphoria, vocalization, hyperactivity, muscle tremors, vomiting and diarrhea, tachycardia, hyperesthesia, panting, hyperthermia, seizures, and  potentially death in severe cases. Data ­reflecting the exact incidence this occurs in companion animals lacks, however it is expected to be less than that experienced in people. Regardless, it is best to avoid mixing TCAs, SSRIs, tramadol, and SNRIs together and avoid administering them with other drugs that may also increase serotonin (e.g. monoamine oxidase inhibitors like selegiline, meperidine, methadone, etc.) unless the patient is carefully monitored for adverse effects (Plumb 2023).

10.7.10  Gabapentinoids: Gabapentin and Pregabalin Gabapentin was originally developed for the treatment of epilepsy in people, but it has since

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been proven useful for treating pain post spinal cord injuries (Davis et al. 2019). Gabapentin is an amino acid molecule that binds to alpha-­2 delta on voltage-­gated calcium channels within the dorsal horn of the CNS to reduce calcium currents, preventing glutamate release in the nociceptive pathways. This is believed to be the main mechanism of action although other studies described inhibitory effects on substance P release in afferent neurons in rats when administered spinally and intraperitoneally (Davis et  al.  2020). Gabapentin is typically used as an adjunctive agent, meaning it is given long term in conjunction with other chronic pain drugs such as NSAIDs, NMDA antagonists, and opioids. The drug is generally well tolerated in dogs and cats with transient sedation being the main clinical side effect. In canines treated with gabapentin for chronic pain, there was an improvement in quality of life. Unfortunately, in cats, there was a deterioration of quality of life yet an increase in perceived comfort was documented by the owners (Siao et al. 2010). Current dosage recommendations for gabapentin as an adjunct analgesic is 3–20 mg/kg PO in canines and felines with as high as 50 mg/kg being documented. These oral dosage regimens are currently recommended for 12 hours yet gabapentin administration every 6–8 hours may be needed to provide adequate concentrations for analgesia (Grubb  2018). In humans, elderly patients with underlying disease states may be profoundly affected and a dosage reduction in the medication may be necessary. This side effect is not yet recorded in geriatric animals at this time. Pregabalin is a more potent successor to gabapentin that has also been investigated for its use in chronic pain states in both people and animals. Studies have shown a successful reduction in clinical signs of central ­neuropathic in dogs ailed by syringomyelia. The mechanism of action mimics that of gabapentin but appears more potent and has a longer half-­life (Papich 2021). Due to the cost burden and controlled substance classification,

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it is less widely used than the less expensive gabapentin. According to Papich 2021, pregabalin dosage is 2–5 mg/kg PO every 8–12 hours in canines. Supportive studies documented a dosage of 4 mg/kg PO every 12 hours as appropriate in healthy dogs (Salazar et al. 2009). For treating felines, a dosage at 4 mg/kg PO provides plasma concentrations above the levels effective for 12 hours. with a half-­life of 10 hours (Papich  2021). More studies are needed to further understand the side effects, proper dosage regimens, and long-­term use for our companion animals.

10.7.11  N-­Methyl-­D-­Aspartate Antagonists Chronic pain states can be maintained and enhanced in part by a state of central sensitization within the CNS that is initiated by NMDA receptor activation. Normally, the NMDA receptor remains blocked by magnesium in individuals who are not in chronic pain states; however, once the NMDA receptor is activated, sodium and calcium ion influx occur within postsynaptic neurons, which activate several second messenger signaling cascades resulting in an increase in pain sensation. NMDA antagonists can be employed to minimize or eliminate the excitability of these neurotransmitters. Their binding to the phencyclidine sites, reduces the noxious stimuli that reach the dorsal horn of the spinal cord affecting the processing and modulation of the pain perceived (McKune  2011). These medications that have been used in clinical settings as adjunctive pain agents include amantadine, ketamine, dextromethorphan, and methadone. Other NMDA receptor antagonists such as memantine, magnesium, xenon, and nitrous oxide have been used experimentally but not in clinical practice as yet. Tramadol may also possess some NMDA antagonist properties, but further investigation into this drug’s mechanism of action is required. Ketamine is a highly effective NMDA antagonist, used intravenously via a continuous rate infusion for patients in hospitalized settings. It

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is recognized to be less effective with visceral vs. somatic pain. In some instances where chronic pain has altered a patient’s behavior this has been a useful treatment to lessen the  hypersensitivity, specifically central ­sensitization or “wind up,” to noxious stimuli. Subcutaneous ketamine therapy is an emerging treatment in veterinary medicine with studies underway. Anecdote suggests a 0.5–1 mg/kg dosage given weekly to monthly may benefit some animals experiencing chronic or difficult to treat pain. This is a subanesthetic dosage that does not typically manifest in behavioral changes or sedation. More recently, similar ketamine therapy has become a selected treatment for depression, chronic pain, and other mental health disorders in humans. For ease of administration, amantadine appears the most attractive NMDA antagonist for long-­term use in companion animals as the  oral counterpart to ketamine (Gruen et al. 2022). It has been shown to be beneficial as an adjunctive pain therapy when combined with NSAID refractory OA pain in dogs. Although pharmacokinetic data is lacking, dosages for dogs and cats is written as 3–5 mg/ kg PO every 12–24 hours with recommendations to start lower. Literature suggests administration every 12 hours may provide more ideal results (Grubb  2018). Gastrointestinal upset is the main clinical adverse effect observed, although there are others, such as tremors, anxiety, ataxia, and hypersalivation.

10.7.12  Neurokinin-­1 Inhibitors Neurokinin-­1 (NK-­1) antagonists, such a maropitant, selectively block NK-­1 receptors (a type of tachykinin receptor) and the subsequent activation of substance P. Substance P is a neurotransmitter and neuromodulator that is important in the process of pain perception as well as in the vomiting reflex. Maropitant is  widely used as an antiemetic for dogs and  cats to manage emesis associated with pancreatitis, gastritis, parvoviral enteritis, and

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chemotherapy-­induced nausea. Literature notes with NK-­1 receptors being present in different areas of the pain pathway, both the ­central nervous system and peripheral tissues, that there is a possibility it would aid in the management of visceral pain, inflammatory responses, stress, and anxiety (Sharun et  al.  2021). While not commonly treated, maropitant has been shown to provide aid in the treatment of “chest pain” secondary to chronic bronchitis in canines and working as an adjunct for maintaining comfort levels in patients receiving cancer and/or hospice care. The authors are cautious not to recommend maropitant for acute of chronic pain at this point in time with the exception of its use for chronic bronchitis in canines.

10.7.13 Bisphosphonates Bisphosphonates (BP) are a class of drugs that prevent the loss of bone mass by blocking osteoclasts (the bone cells responsible for the breakdown of bone), thus stabilizing bone destruction and potentially helping to manage pain. In humans, BPs have supported patients with postmenopausal osteoporosis, osteogenesis imperfecta, multiple myeloma, metastatic breast as well as prostatic cancer (Suva et  al.  2021). Similarly, bisphosphonates have been used in companion animals for alleviating bone pain associated with bone-­destructing diseases (predominantly OSA in dogs and navicular disease in horses) and treating hypercalcemia in several other species. Regrettably, these analgesic agents are not without consequences. In humans, there have been occurrences of atypical femur fractures and osteonecrosis of the jaw with long-­term therapy (Suva et al. 2021). Likewise, these adverse events are also reflected in our veterinary patients after prolonged usage. For instance, in felines, there have been jaw osteonecrosis as well as bilateral patella fractures and oral mucosal ulcerations along with ­mandibular bone exposure in canines (Suva et al. 2021). At this time, it remains an adjunctive option for

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additional analgesia and is often administered as follows: pamidronate 1–2 mg/kg diluted in 250 ml 0.9% NaCl and administered IV over 2 hours. This is combined with standardized palliative radiation therapy, an NSAID, and doxorubicin or as a single agent with an NSAID. Before considering BPs for the treatment of chronic pain in any patient, a veterinary oncologist should be consulted to discuss the risk versus benefits of this potential treatment. Further studies are needed to appreciate BP efficacy in the setting of chronic pain.

10.7.14  Anti-­NGF, Monoclonal Antibodies Solensia® (frunevetmab) and Librela® (bedinvetmab) are monoclonal antibodies administered subcutaneously once a month to alleviate the pain associated with OA. Each drug is species specific and should only be used in the species they are labeled for. Anti-­NGF monoclonal antibodies (mAbs) offer a new modality for pain relief. Recent human trials and now canine and feline studies have shown that these mAbs can effectively treat moderate to severe pain in OA-­affected joints, with results sometimes surpassing those of traditional pain relievers like NSAIDs or opioids.

10.7.15  Nutraceuticals and Animal Health Supplements Nutraceuticals are a combination of the words nutrition and pharmaceutical. They come in many forms, including dietary supplements, specific diets, and herbal products. Many “joint supplements” are available over the counter and often include glucosamine and chondroitin sulfate. Several other products often ­contain ingredients like avocado/soybean unsaponifiable, methylsulfonylmethane (MSM), and silymarin. Despite weak clinical trial evidence to support the use of most nutraceuticals, their popularity persists (Aragon et  al.  2007; McCarthy et  al.  2007; Thomson et  al.  2008; McKenzie  2010). Please see

10.9 ­Conclusio

Chapter 17 for nutraceutical and ­supplements that may be effective in pain management.

10.8 ­Lifestyle Modifications 10.8.1  Weight Loss and Appropriate Nutrition Similarly to humans, a large portion of the pet population is overweight or obese. Per the AAHA 2022 Guidelines for Pain Management, adipose tissues can worsen pathologies of inflammatory conditions, OA, the hypersensitization of pain, and many other conditions by secreting mixed cytokines throughout the body. These cytokines in human research have been linked to amplifying the progression of OA in joints, worsening the patient’s discomfort  – both weight-­bearing and non-­weight-­bearing joints. In our veterinary patients, these chronic pain conditions worsened by obesity (e.g. elbow dysplasia or hip dysplasia, etc.) can be greatly improved by having the patient achieve an appropriate weight (Impellizeri et  al.  2000; Mlacnik et  al.  2006; Marshall et  al.  2009; Marshall et  al.  2010). For more on nutrition please see Chapter 17.

10.8.2  Routine Exercise and Physical Therapy For many patients with chronically painful musculoskeletal conditions, regular mild to moderate low-­impact exercise and physical therapy can be beneficial. The benefits are profoundly reflected in human medicine with minimal, yet parallel responses seen in companion animals with mobility diseases (Mlacnik et al. 2006). The varied modalities existing for companion animal rehabilitation include but are not limited to underwater treadmills, land-­based treadmills, hydrotherapy tubs, deep-­tissue ultrasound, hydrotherapy, low-­level laser therapy with electrical stimulation, extracorporeal shockwave ­therapy, class IV laser therapy, therapeutic exercise, passive range of motion, stretching,

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massage, joint mobilization, myofascial release, and thermal tissue modification. According to the AAHA Pain Management Guideline panel, rehabilitative therapy should be considered as a vital part of the comprehensive wellness plan in any patient affected by acute or chronic pain (Gruen et  al.  2022). Further information is available to the reader in Chapter 16.

10.8.3  Thinking “Out of the Box” through Environment Modifications Sometimes, the simplest things can have profound effects. Small creative changes to a companion animal’s life can have a positive impact on improving patient comfort and quality of life. Something as simple as ensuring a pet has adequate padding where they sleep or spend most of their time can be beneficial. Other environmental modifications like avoiding stairs and slippery floors or creating ramps for patients to get into and out of the car or on and off of the bed can be helpful. Moving food bowls or litter boxes into places that are easier for cats to access can make for increased patient comfort. Lots of older dogs find household floors slippery, and the addition of just a few rugs can allow for more sure footing and less muscle strain. Feeding a dog with elbow dysplasia at 6–12 in. off the ground can redistribute a dog’s weight off its thoracic limbs. Feeding soft food over a hard kibble can be useful in patients with oral pain or neoplasia. Investing in a “Help Em Up™ Harness” (Blue Dog Designs, Denver, CO) can vastly improve pelvic support and mobility in many older dogs.

10.9 ­Conclusion As veterinary professionals it is our responsibility to continue supplying our “toolbox” with agents or techniques that can help relieve the pain and suffering of our patients. It is pertinent that we remain current on advances made in veterinary medicine for the treatment of any type of pain.

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­References Adrian, D., King, J.N. et al. (2021). Robenacoxib shows efficacy for the treatment of chronic degenerative joint disease-­associated pain in cats: a randomized and blinded pilot clinical trial. Scientific Reports 7721: https://doi.org/ 10.1038/s41598-­021-­87023-­2. Alves, J.C., Santos, A., Jorge, P., and Lafuente, P. (2022). A multiple-­session mesotherapy protocol for the management of hip osteoarthritis in police working dogs. American Journal of Veterinary Research 1–8. https://doi.org/10.2460/ajvr.22.08.0132. American Psychiatric Association Division of Research (2013). Highlights of Changes from DSM-IV to DSM-5. FOCUS 11 (4). https://doi. org/10.1176/appi.focus.11.4.525. Aragon, C.L., Hofmeister, E.H., and Budsberg, S.C. (2007). Systematic review of clinical trials of treatments for osteoarthritis in dogs. Journal of the American Veterinary Medical Association 230 (4): 514–521. Davis, K.N., Hellyer, P.W. et al. (2019). Qualitative study of owner perception of chronic pain in their dogs. Journal of the American Veterinary Medical Association 254 (1): https://doi.org/10.2460/javma.254.1.88. Davis, L.V., Hellyew, P.W. et al. (2020). Retrospective study of 240 dogs receiving gabapentin for chronic pain relief. Journal of Veterinary Medicine and Research 7 (4): 1194. Dominquez-­Oliva, A., Casa-­Alvarado, A. et al. (2021). Clinical pharmacology of tramadol and tapentadol, and their therapeutic efficacy in different models of acute and chronic pain in dogs and cats. Journal of Advanced Veterinary and Animal Research 8 (3): 404–422. https:// doi.org/10.5455/javar.2021.h529. Dowdy, S.M. (2020). From periphery to perception: the pathway to pain. DVM 360 115 (8). Gowan, R.A., Lingard, A.E., Johnston, L. et al. (2011). Retrospective case—­control study of the effects of long-­term dosing with

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meloxicam on renal function in aged cats with degenerative joint disease. Journal of Feline Medicine and Surgery 13 (10): 752–761. https://doi.org/10.1016/j. jfms.2011.06.008. Gowan, R.A., Baral, R.M., Lingard, A.E. et al. (2012). A retrospective analysis of the effects of meloxicam on the longevity of aged cats with and without overt chronic kidney disease. Journal of Feline Medicine and Surgery 14 (12): 876–881. https://doi.org/ 10.1177/1098612x12454418. Greene, S.A. (2010). Chronic pain: pathophysiology and treatment implications. Topics in Companion Animal Medicine 25 (1): 5–9. https://doi.org/10.1053/j.tcam.2009. 10.009. Grubb, T. (2018). Gabapentin and amantadine for chronic pain: is your dose right? Today’s Veterinary Practice 8 (6). Gruen, M.E., Lascelles, B.D. et al. (2022). 2022 AAHA pain management guidelines for dogs and cats. Journal of the American Animal Hospital Association 58 (2): 55–76. https://doi. org/10.5326/JAAHA-­MS-­7292. Guedes, A.G.P., Meadows, J.M., Pypendop, B.H., and Johnson, E.G. (2018). Evaluation of tramadol for treatment of osteoarthritis in geriatric cats. Journal of the American Veterinary Medical Association 252 (5): 565–571. https://doi.org/10.2460/javma.252.5.565. Hunt, J.R., Dean, R.S. et al. (2015). (2015) an analysis of the relative frequencies of reported adverse events associated with NSAID administration in dogs and cats in the United Kingdom. Veterinary Journal 206 (2): 183–190. https://doi.org/10.1016/j.tvjl.2015. 07.025.Epub. Impellizeri, J.A., Tetrick, M.A., and Muir, P. (2000). Effect of weight reduction on clinical signs of lameness in dogs with hip osteoarthritis. Journal of the American Veterinary Medical Association 216 (7): 1089–1091.

 ­Reference

Innes, J.F., Clayton, J., and Lascelles, B.D. (2010). Review of the safety and efficacy of long-­term NSAID use in the treatment of canine osteoarthritis. The Veterinary Record 166: 226–230. Jordan, D.G. and Ray, J.D. (2012). Management of chronic pain in cats. Today’s Veterinary Practice. November/December 2012. Koffel, E., Krebs, E.E., Arbis, P.A. et al. (2016). The unhappy triad: pain, sleep complaints, and internalizing symptoms. Clinical Psychological Science: A Journal of the Association for Psychological Science 4 (1): 96–106. Kukanich, B. and Spade, J. (2012). Pharmacokinetics of hydrocodone and hydromorphone after oral hydrocodone in healthy Greyhound dogs. Veterinary Journal 196 (2): 266–268. Lascelles, B.D.X., Brown, D.C. et al. (2019). Measurement of chronic pain in companion animals: priorities for future research and development on discussion from the pain in animals workshop (PAW). The Veterinary Journal 2017 252: 105370. https://doi.org/10.1016/j.tvjl.2019.105370. Madden, M., Gurney, M., and Bright, S. (2011). Amantadine, an N-­methyl-­D -­aspartate antagonist, for treatment of chronic neuropathic pain in a dog. Veterinary Anaesthesia and Analgesia 41 (4): 440–441. https://doi.org/10.1111/vaa.12141. Marshall, W., Bockstahler, B., Hulse, D., and Carmichael, S. (2009). A review of osteoarthritis and obesity: current understanding of the relationship and benefit of obesity treatment and prevention in the dog. Veterinary and Comparative Orthopaedics and Traumatology 22 (5): 339–345. Marshall, W.G., Hazewinkel, H.A., Mullen, D. et al. (2010). The effect of weight loss on lameness in obese dogs with osteoarthritis. Veterinary Research Communications 34 (3): 241–253. Mathews, K., Kronen, P.W. et al. (2014). Guidelines for Recognition, Assessment, and

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Treatment of Pain. WSAVA Global Veterinary Community. McCarthy, G., O’Donovan, J., Jones, B. et al. (2007). Randomised double-­blind, positive-­ controlled trial to assess the efficacy of glucosamine/chondroitin sulfate for the treatment of dogs with osteoarthritis. Veterinary Journal 174 (1): 54–61. McKenzie, B.A. (2010). What is the evidence? There is only very weak clinical trial evidence to support the use of glucosamine and chondroitin supplements for osteoarthritis in dogs. Journal of the American Veterinary Medical Association 237 (12): 1382–1383. McKune, C. (2011). N-­methyl-­D-­aspartate (NMDA) receptor antagonists (proceedings). https://www.dvm360.com/view/n-­methyl-­ d-­aspartate-­nmda-­receptor-­antagonist-­ proceedings (accessed 5 June 2024). Mlacnik, E., Bockstahler, B.A., Müller, M. et al. (2006). Effects of caloric restriction and a moderate or intense physiotherapy program for treatment of lameness in overweight dogs with osteoarthritis. Journal of the American Veterinary Medical Association 229 (11): 1756–1760. Monitto, C.L., Hsu, A., Gao, S. et al. (2017). Opioid prescribing for the treatment of acute pain in children on hospital discharge. Anesthesia & Analgesia 125 (6): 2113–2122. https://doi.org/10.1213/ ane.0000000000002586. Monteiro, B.P. (2020). Feline chronic pain and osteoarthritis. Veterinary Clinics of North America: Small Animal Practice 50 (4): 769–788. https://doi.org/10.1016/j. cvsm.2020.02.003. Epub 2020 Apr 27. Monteiro, B.P., Lascelles, B.D.X. et al. (2022). WSAVA guidelines for the recognition, assessment, and treatment of pain. Journal of Small Animal Practice 64 (4): 177–254. https://doi.org/10.1111/jsap.13566. Moraczewski, J., Aedma, K., and K. (2022). Tricyclic Antidepressants. National Library of Medicine. StatPearls Publishing.

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Norkus, C., Rankin, D., and Kukanic, B. (2015). Pharmacokinetics of intravenous and oral amitriptyline and its active metabolic nortriptyline in greyhound dogs. Veterinary Anaesthesia and Analgesia 42 (6): 580–589. https://doi.org/10.1111/vaa.12248. Epub 2015 Feb 14. PMID: 25683584. Obuchowicz, E., Kowalski, J., Labuzek, K. et al. (2006). Amitriptyline and nortriptyline inhibit interleukin-­1 release by rat mixed glial and microglial cell cultures. International Journal of Neuropsychopharmacology 9 (1): 27–35. Orhurhu, V., Orhurhu, M.S., Bhatia, A., and Cohen, S.P. (2019). Ketamine infusions for chronic pain: a systematic review and meta-­analysis of randomized controlled trials. Anesthesia & Analgesia 129 (1): 241–254. https://doi.org/10.1213/ANE. 0000000000004185. Papich, M.G. (2021). Pregabalin. In: Papich Handbook of Veterinary Drugs, 5e, 774–776. https://doi.org/10.1016/B978-­0-­323-­70957-­6. 00449-­0. Patil, S. and Anitescu, M. (2012). Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-­year retrospective analysis. Pain Medicine 13 (2): 263–269. https://doi.org/10.1111/j.1526-­4637.2011. 01241.x. Plessas, I.N., Volk, H.A., and Kenny, P.J. (2013). Migraine-­like episodic pain behavior in a dog: can dogs suffer from migraines? Journal of Veterinary Internal Medicine 27 (5): 1034–1040. https://doi.org/10.1111/jvim.12167. Plumb (2023). Plumb’s Veterinary Drug Handbook. Wiley-Blackwell Publishing. Rusbridge, C. (2020). New considerations about Chiari-­like malformation, syringomyelia and their management. In Practice 42 (5): 252–267. https://doi.org/10.1136/inp.m1869. Salazar, V., Dewey, C.W., Schwark, W. et al. (2009). Pharmacokinetics of single-­dose oral pregabalin administration in normal dogs. Veterinary Anaesthesia and Analgesia 36 (6): 574–580.

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Sharun, K., Jambagi, K. et al. (2021). Clinical applications of substance P (neurokinin-­1 receptor) antagonist in canine medicine. Archives of Razi Institute 76 (5): 1175–1182. https://doi.org/10.22092/ari.2021.356171.1797. Siao, K.T., Pypendop, B.H., and IIkiw, J.E. (2010). Pharmacokinetics of gabapentin in cats. American Journal of Veterinary Research 71 (7): 817–821. Steagall, P. (2015) Analgesic tools in small animal anesthesia. World Small Animal Veterinary Association World Congress Proceedings 2015. Suva, L.J., Cooper, A. et al. (2021). Bisphosphonates in veterinary medicine: the new horizon for use. Bone 142: https:// doi.org/10.1016/j.bone.2020.115711. Tai, Y.H., Tsai, R.Y., Lin, S.L. et al. (2009). Amitriptyline suppresses neuroinflammation-­ dependent interleukin-­10-­p38 mitogen activated protein kinase-­heme oxygenase-­1 signaling pathway in chronic morphine infused rats. Anesthesiology 110 (6): 1379–1389. Tardiolo, G., Bramanti, P., and Mazzon, E. (2019). Migraine: experimental models and novel therapeutic approaches. International Journal of Molecular Sciences 20 (12): 2932. https://doi.org/10.3390/ijms20122932. Thomson, R.M., Hammond, J., Ternent, H.E., and Yam, P.S. (2008). Feeding practices and the use of supplements for dogs kept by owners in different socioeconomic groups. Veterinary Record 163 (21): 621–624. Today’s Veterinary Practice – no author noted (2013). Assessing the Chronic Pain in Dogs. https://todaysveterinarypractice.com/ pain_management/assessing-­chronic-­pain-­in-­ dogs (accessed 5 June 2024). United States Food and Drug Adminstration (2023). Information about the boxed warning on meloxicam labels regarding safety risks in cats. https://www.fda.gov/animal-veterinary/ product-safety-information/informationabout-boxed-warning-meloxicam-labels-

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regarding-safety-risks-cats (accessed 5 June 2024) Vuralli, D., Wattiez, A.-­S., Russo, A.F., and Bolay, H. (2019). Behavioral and cognitive animal models in headache research. The Journal of Headache and Pain 20 (1): https://doi.org/ 10.1186/s10194-­019-­0963-­6. Wiseman-­Orr, M.L., Nolan, A.M., Reid, J., and Scot, E.M. (2004). Development of a questionnaire to measure the effects of chronic pain on health-­ related quality of life in dogs. American Journal of Veterinary Research 65: 1077–1084.

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Wiseman-­Orr, M., Scott, E.M. et al. (2006). Validation of a structure questionnaire as an instrument to measure chronic pain in dogs on a basis of effects on health-­related quality of life. American Journal of Veterinary Research 67 (11): 1826–1836. Yong, R.J., Mullins, P.M., and Bhattacharyya, N. (2022). Prevalence of chronic pain among adults in the United States. The Journal of the International Association for the Study of Pain 163 (2): 328–333. https://doi.org/ 10.1097/j.pain.0000000000002291.

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11 Analgesia for Shelter Medicine and Trap–Neuter–Return Programs Anne Marie McPartlin1 and Erin Spencer1,2 1 2

Rural Area Veterinary Services, Humane Society of the United States, Watertown, New York, USA Veterinary Emergency Group, Derry, New Hampshire, USA

11.1 ­Introduction Shelter medicine is a crucial aspect of veterinary medicine that encompasses a variety of clinical settings to address access to care challenges, pet overpopulation, and animal welfare. Its importance and relevance within communities has given rise to advances in low-­cost, high-­ case care to the point where shelter medicine is part of the veterinary curricula and specialty certifications are being developed. Examples where shelter medicine is applied include brick-­and-­mortar shelters, low/no cost ­clinics,  high-­quality/high-­volume spay-­neuter (HQHVSN) clinics, and mobile army surgical hospital (MASH)-­style field clinics (Figures 11.1 and 11.2). Within these types of organizations, the primary focus has been on providing spay/neuter services; however, animals often present requiring additional procedures that may involve a more individualized analgesic plan. The authors encourage the use of other chapters in this book to provide additional information on analgesia for specific procedures where warranted. Multifactorial considerations come into play when managing patients in shelter medicine. These include but are not limited to pediatrics, patients exhibiting fear, anxiety, or stress (FAS),

unknown medical histories or preliminary diagnostics, and patients requiring multiple procedures. In many clinical settings, clients are often facing financial burdens that may dictate the patient treatment plan. As shelter and outreach programs attempt to keep animals and families together, an incremental veterinary care approach to deliver the best possible outcome for each patient through individualism and experience-­based medicine is essential (Brown et al. 2021). Limited resource settings have been found beneficial in minimizing cost to clients while focusing treatment plans that have maximum benefit for the patient. With a focus on keeping patients comfortable and mitigating FAS, we can provide a high level of care that elevates the trust of our clients and communities and can actually reduce costs associated with additional top-­offs or secondary complications.

11.2 ­Multimodal Analgesia With an understanding of the pain pathway, and physiological response to pain, drug interventions can be tailored to meet the needs of each patient with considerations for severity and duration of pain experienced. By targeting different points along the nociceptive pathway,

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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Figure 11.1  Rural area veterinary services (RAVS) clinic 2022. Source: Courtesy of Anne Marie McPartlin.

Figure 11.2  Rural area veterinary services (RAVS) clinic 2022; room setup. Source: Courtesy of Anne Marie McPartlin.

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11.2 ­Multimodal Analgesi

it can enhance the effectiveness and reduce the dose of any one drug. Drug classes typically available in a shelter setting include: ●● ●●

●● ●● ●●

Opioids Nonsteroidal anti-­inflammatory drugs (NSAIDs) N-­methyl-­D-­aspartate (NMDA) antagonists Alpha-­2 agonists Local anesthetics

It’s encouraged to consider all of these drug classes when developing a multimodal analgesic plan.

11.2.1  Opioids In shelter medicine, opioids are often used in anesthetic drug cocktails such as TTD (­t elazol/butorphanol/dexmedetomidine) and DTK (dexmedetomidine/butorphanol/ ketamine), which allow for premedication and induction agents to be administered in one injection (see Table 11.3 for more information on anesthetic drug combinations). The benefit of one injection can help in reducing FAS in animals undergoing procedures. There are a variety of combinations; any of the pure agonist opioids can be interchanged with butorphanol to achieve the desired effect particularly for procedures entering a body cavity or are more painful in general. Buprenorphine has a maximal efficacy onset of approximately 45 minutes, the timing of which should always be a consideration when determining its use as a premedication or postoperative analgesic. Buprenorphine has classically been described as effective for mild to moderate pain, but newer data support buprenorphine as providing adequate analgesia with severe pain (e.g. limb amputation) in cats when administered at the higher doses every 6–8 hours. Simbadol™ is a Food and Drug Administration (FDA)-­approved 24 hours buprenorphine injection that has a higher concentration (1.8 mg/ml), allowing for a

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smaller volume to be administered subcutaneously. Simbadol at regular dosages of less concentrated buprenorphine can also be used instead of carrying two forms of buprenorphine and may be more cost effective. However, decreasing the dosage and administering IV, IM, SC, OTM, or IN will not provide 24 hours of analgesia but the typical 4–6 hours. For severe pain and to lower inhalant anesthesia concentration, opioids are useful considerations as continuous rate infusions when the equipment is available to administer safely (fluid pump + burette or syringe pump). They can be administered as sole CRIs or in combination with drugs like ketamine or lidocaine. Where butorphanol is the only opioid available, it becomes even more critical to use additional medications such as NMDA antagonists, local anesthetics and/or α-­2 agonists to meet the required analgesic effect. See Table 11.1 for opioid dosing recommendations.

11.2.2  Nonsteroidal Anti-­inflammatory Drugs (NSAIDs) Due to their analgesic and anti-­inflammatory properties, NSAIDs play a large role in shelter settings as part of a multimodal analgesic plan. Side effects associated with the use of NSAIDs are most commonly related to GI issues such as ulcers and general upset, with less adverse effects on renal and hepatic systems. The timing of NSAID administration is a consideration. Given preoperatively, NSAIDs significantly reduce postoperative inflammation resulting in better analgesia. One of the biggest considerations with the use of NSAIDs perioperatively is the risk of acute kidney injury should the patient experience hypotension during anesthesia. The onset time for NSAIDs is 30–60 minutes, so this does not tend to be an issue in a shelter setting where surgical procedures are performed quickly. However, if blood pressure monitoring during anesthesia is unavailable, it may be wiser to administer NSAIDs postoperatively.

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More studies need to be performed to determine the effects of one-­time NSAID use in animals undergoing surgery. There has been some evidence to suggest that chronic use of meloxicam in cats with International Renal Interest Society (IRIS) stage 2–3 CKD does not have a significant effect on renal values or longevity (Gowan et al. 2012). Single-­dose

NSAIDs (see Tables  11.2 and 11.3) for acute pain in cats may have an analgesic effect for 18–20 hours (Sparkes et al. 2010), making it a valuable option where postoperative analgesic dosing may be difficult due to animal handling or ability of caregivers to administer medications, or when controlled substances are unavailable.

Table 11.1  Common opioids found in shelter medicine. Drug

Class

Use

Considerations

Dosage

Morphine

Pure agonist

Moderate to severe pain

May cause vomiting and defecation when used for premedication. May cause histamine release when administered IV.

Dogs 0.25–1.0 mg/kg IM or slowly IV Cats 0.1–0.3 mg/kg IM or slowly IV

Hydromorphone

Pure agonist

Moderate to severe pain

Similar to morphine but no histamine release.

Dogs 0.1–0.2 mg/kg IM or IV Cats 0.1 mg/kg IM or IV

Methadone

Pure agonist

Moderate to severe pain

Buprenorphine

Partial mu agonist

Moderate pain

Longer duration than pure agonist opioids. Duration is dose dependent. Prolonged onset.

Dogs and cats 0.02–0.06 mg/kg IM, IV, OTM   Cats OTM dosing 0.03–0.06 mg/kg (if unable to give injection)

Butorphanol

Kappa agonist, mu antagonist

Light sedation, mild pain

Used mostly for sedation, short duration of action; ceiling effect on analgesia but can provide adequate analgesia when combined with an alpha-­2 agonist for minor procedures. This is best used for procedures that do not enter a body cavity, manipulate bone, or would be considered moderately painful.

Dogs and cats 0.2–0.4 mg/kg IM or IV

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Dogs and cats 0.1–1.0 mg/kg IM or IV Cats OTM dosing has been shown effective (Dose may need to be increased based on individual response.)

11.2 ­Multimodal Analgesi

Table 11.2  Common NSAIDs used in shelter medicine (Monteiro et al. 2022). Drug

Considerations

Dosage

Meloxicam

Injectable solution FDA approved for one-­time use in cats. EU approved oral dose in cats at 0.05 mg/kg PO. Loading dose of 0.2 mg/kg once recommended for dogs. There is evidence to show that 0.02 mg/kg is well tolerated in cats for chronic use.

Dogs 0.2 mg/kg/d, IV, SC once only Dogs 0.1 mg/kg every 24 hr Cats 0.2–0.3 mg/kg SC once only Cats 0.05 mg/kg PO every 24 hours up to 5 days

Carprofen

EU approved short-­term use in cats. FDA approved use in dogs. Hepatopathies have been reported in dogs (in particular Labradors).

Dogs 2.2 mg/kg every 12 hours or 4.4 mg/kg every 24 hours PO, SC, or IV up to 4 days Cats 2–4 mg/kg SC or IV once only

Robenacoxib (Onsior™)

Selective COX-­2 inhibitor. Well tolerated in cats. May be cost-­ prohibitive in some shelter settings.

3 days maximum use Dogs 2 mg/kg PO or SC every 24 hours Cats 2 mg/kg SC every 24 hours Cats 1–2 mg/kg PO every 24 hours

Ketoprofen

Side effects similar to other NSAIDs. Hepatopathies and renal disease have been reported in animals.

Cats and dogs 2 mg/kg SC, IV, IM once only Cats and dogs 1 mg/kg PO every 24 hours for up to 4 days

Grapiprant (Galliprant™) *Non-­typical NSAID*

Available in tablet form only for use in dogs. Well tolerated with reduced GI side effects associated with other NSAIDs. May be cost prohibitive in some shelter settings.

Dogs 2 mg/kg PO every 24 hours

Table 11.3  Pros and cons of reconstituting an analgesic drug combination in a single bottle. Pros

Cons

Ease of logging

Unable to adjust dosages of individual drugs within the cocktail

Reduced risk of contamination (single multi-­use bottle as opposed to 3+ bottles)

Reliability of concentration when mixing multiple drugs

Single volume drawn up simplifies process

Stability of drugs (may have reduced shelf life once reconstituted)

There is no guarantee that drawn up volumes contain equal portions of each drug when a large batch of a mixed solution is made. Regular inverting or gentle rocking should be performed regularly to prevent separation of mixed drugs.

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11.2.3  NMDA Antagonists NMDA antagonists such as ketamine and tiletamine solutions (a component in Telazol™), and to an extent methadone, are often already a part of anesthetic protocols found in shelter medicine. NMDA receptor activation is one of the main causes of central sensitization, producing a painful windup effect. Drugs like ketamine antagonize NMDA receptors to help mitigate the risk of hyperalgesia. Ketamine has also been shown to reduce systemic inflammation without affecting local healing processes (Loix et al. 2011). Ketamine can be part of the anesthetic plan or administered for analgesia using micro doses or as a CRI. Ketamine at a dosage of 0.5–1 mg/kg IV is an effective “top-­off” analgesic that can be administered intraoperatively to avoid having to increase inhalant anesthesia during a routine procedure like spay or neuter.

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11.2.4  Alpha-­2 Adrenoceptor Agonists Alpha-­2 (α-­2) agonists, including medetomidine and dexmedetomidine, are commonly used in shelter medicine as part of anesthetic drug cocktails. In addition to providing sedation, analgesia, and muscle relaxation, they have a safety benefit of being fully reversible using the antagonist atipamezole. They can have significant cardiovascular side effects, with the most notable being reduced cardiac output. Drug side effects should be a consideration if used in animals with known cardiovascular disease. Xylazine was once more commonly used in small animal anesthesia, but it has a high rate of adverse effects in dogs and cats and is now being added as a scheduled drug in some states. Dexmedetomidine and medetomidine provide more analgesia than xylazine and are not associated with significant adverse effects when appropriate dosages are utilized. The generic formulations have made these drugs popular in a shelter setting due to decreased cost. As with ketamine, a dosage of dexmedetomidine, 1 mcg/kg IV administered intraoperatively can be an effective “top-­off” analgesic. It can also be used postoperatively on patients experiencing emergence delirium at a dosage of 1–2 mcg/kg IV. The 500 mcg/ml (0.5 mg/ml) concentration of dexmedetomidine results in very small volumes at the micro doses. Dexmedetomidine also comes in 100 mcg/ml (0.1 mg/ml) concentration, but it may be cost-­prohibitive to stock both drug concentrations. The 500 mcg/ml (0.5 mg/ml) concentration can be diluted by taking 1-­part dexmedetomidine to 9 parts diluent to produce a 50 mcg/ml concentration. Dexmedetomidine can also be administered as  a CRI on a syringe pump at a dose of 0.5–2 mcg/kg/h (e.g. limb amputation). There is also evidence that alpha-­2 agonists work synergistically with opioids (Chabot-­ Doré et  al.  2015) and local anesthetics (Grubb et al. 2020) to provide greater analgesia with longer duration of effect. It’s important to note that if alpha-­2 agonists are reversed due to

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unwanted side effects, the analgesia will be reversed as well.

11.2.5  Local Anesthetics Local anesthetics are inexpensive and not scheduled, making them a valuable tool when developing a multimodal analgesic plan. A number of local analgesic techniques can be implemented in shelter medicine that will not have a detrimental effect on the timing of clinic flow. Testicular blocks, incisional line blocks, peritoneal lavage, and incisional splash blocks have a short learning curve and can be easily administered even in fast-­paced environments. Calculated dosing charts can assist with drawing up local anesthetics in advance and avoid the risk of toxicity (Grubb and Lobprise 2020). For doses and other considerations of local anesthetics, please see Chapter 6. Dental blocks and epidurals can also be considered depending on the services provided. They take more training to administer; however, once proficient, they can be a valuable addition to pain control without disrupting clinic flow. With availability of local anesthetics being variable, it may be worth considering the use of a more expensive drug such as bupivacaine liposome injectable suspension (Nocita™). It has been shown to provide 72 hours of analgesia when injected locally to the affected area. Nocita™ is approved for use in cats and dogs and may be beneficial for animals having same-­day discharges where further analgesic administration would not be possible. An important consideration is that this drug is preservative-­free requiring the contents to be drawn up with aseptic technique and used within a 4-­day period (Carlson et al. 2020). It can cautiously be administered where regular bupivacaine was administered due to the potential of toxicosis. Nocita™ can also be volume expanded with saline or Lactated Ringers solution at a ratio of 1:1 without losing efficacy and expanding the number of doses in a vial.

11.3 ­HQHVSN and TNR Program

11.2.6  Adjunct Therapies Animals in any clinical setting often experience FAS while being housed or hospitalized. FAS can cause the release of stress hormones that have a profound effect on body function resulting in signs of gastrointestinal disturbance, weakened immune system, and delayed healing. The psychological impact can be intense for an animal and may lead to a life-­long struggle to be able to handle a patient. It is our responsibility to use resources to help mitigate FAS and allow for the best possible experience for each patient. Low-­stress-­handling techniques can help reduce anxiety triggers and provide a safer environment for the team (Figure  11.3). Programs offered by the American Association of Feline Practitioners and organizations such as Fear Free™ help train staff in these concepts. Trazodone and

Figure 11.3  The animal holding area for dogs and cats should contain visual barriers to separate cat traps, dog kennels and other cages. This will help reduce FAS and help promote a quieter, calmer environment. Source: Courtesy of Anne Marie McPartlin.

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gabapentin are inexpensive and highly effective anxiolytics. Trazodone can be administered at 3–10 mg/kg PO 30–120 minutes before handling. It is very bitter tasting so it’s usually difficult to administer to cats. Gabapentin is dosed at 10–40 mg/kg PO for dogs and 10–20 mg/kg for cats or 50–100 mg/cat 1–2 hours prior to handling (Becker 2022). Dogs with severe FAS may benefit from the administration of both trazodone and gabapentin.

11.3 ­HQHVSN and TNR Programs HQHVSN and trap–neuter–return (TNR) programs are fast-­paced clinical settings managing a large volume of patients on a daily basis. To provide added safety and maintain efficiency throughout the clinic, it becomes essential in these settings to implement drug charts/Excel sheets for easy reference, simplified yet accurate drug logs to encourage use compliance by staff and assign well-­defined roles to each team member (Figures 11.4 and 11.5). Many high-­volume anesthetic protocols involve cocktails of drugs to allow for premedication and induction agents to be administered in one injection. Many drugs within these cocktails are Drug Enforcement Agency Class II–IV controlled substances such as opioids, dissociative agents, and benzodiazepines that need to be managed with the same scrupulous attention as in any practice. This includes maintaining disposition logs for receiving and distributing drugs for use within the practice, individual drug logs and medical records for each patient, secure storage, and regular drug inventory confirmation. In high-­traffic programs where multiple people may be handling controlled substances, it’s helpful to have a single dedicated individual assigned to drawing up drugs and logging them out as well as a controlled substances manager who maintains ordering, receiving, and distribution of all controlled substances. One example of logging TTD (Telazol™, butorphanol, dexmedetomidine) is to indicate

283

Figure 11.4  Example of single agent drug log. Source: Courtesy of Anne Marie McPartlin.

Figure 11.5  Example of multi-­agent drug log. Source: Courtesy of Anne Marie McPartlin. 本书版权归John Wiley & Sons Inc.所有

11.4 ­Rabbit

the volume of butorphanol used to reconstitute the vial of Telazol on the butorphanol log sheet then identify the log sheet associated with that bottle of Telazol as being “TTD” and log volumes for each patient subsequently when being used. Each program needs to assess the best system to put into action for managing controlled substances that satisfy state and federal requirements, maintain accuracy, and keep clinic flow running efficiently.

11.4 ­Rabbits Being able to recognize pain in rabbits can be difficult. To help provide an adequate baseline for behavior, rabbits should be placed in a quiet area, away from cats and dogs. Once a baseline is established, further observations should be made to look for signs of pain, such as wincing,

aggressive behavior, or increased licking (Guzman  2023). Ideally, observations should be made from a position where the observer cannot be seen to avoid freezing behavior, which can hide signs of pain. Pain scales can be used to identify pain in rabbits. Both the Bristol Rabbit Pain Scale and Rabbit Grimace Scale are two examples of such scales, see Chapter 4 (Guzman, 2023; Benato et al. 2022; Miller et al. 2022). Opioids, NSAIDS, local anesthetics, α-­2 agonists, and other drugs can all be considered part of a pain management protocol in rabbits. Table 11.4 provides dosing guidelines. Utilizing a multimodal analgesia approach is not only beneficial but, through the ability to use lower doses of individual drugs, can decrease potential adverse effects of some drugs. Rabbits are prone to ileus. While there is conflicting evidence, at least one study did

Table 11.4  Analgesic drug doses for rabbits. Drug

Dosage

Route

Considerations

Buprenorphine

0.03–0.1 mg/kg q 4–6 hr

IV, IM, IN

While 0.1 mg/kg is a published high-­end dosage, some resources consider 0.05 mg/kg as a more appropriate high-­end dosage. Use caution with higher dosage.

Buprenorphine sustained release

0.12 mg/kg q 72 to 96 hr

SC

May cause sterile abscesses.

Butorphanol

0.1–1 mg/kg q 2–4 hr

IV, IM

Fentanyl

15–60 mcg/kg/hr (intra-­op CRI) 1.25–5 mcg/kg/hr (post-­op CRI)

IV IV

Methadone

0.2 mg/kg q 4–6 h

IV, IM

Tramadol

10–20 mg/kg q 8–12 hr

PO

Meloxicam

1 mg/kg q 24 hr 0.5–1 mg/kg q 12 hr

SC, PO

Lidocaine

50–100 mcg/kg/min (CRI) Loading dose 1–2 mg/kg

IV

Gabapentin

15–30 mg/kg q 8–12 hr 25 mg/kg q 8–12 hr

PO

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Methadone works very well in rabbits. If analgesia in moderate-­to-­severe pain situations is needed, it should be considered. Meloxicam is the most commonly used NSAID in rabbits. If needed, dosing can go to 2 mg/kg for short periods of time.

Rabbits generally tolerate the higher end of the dosage range of gabapentin well.

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show a correlation between a single dose of morphine (10 mg/kg) or butorphanol (5 mg/kg) and decreased gastrointestinal motility (Deflers et al. 2022). It is important to note that this was a temporary decrease, and no prolonged ileus was observed. By using a multimodal approach, the benefits of opioids can still be utilized while minimizing the risk of hypomotility or ileus. Intratesticular blocks are a quick, easy technique that can be incorporated into a HV setting to further decrease doses of opioids and minimum alveolar concentration (MAC). Lidocaine and bupivacaine are the most commonly used local anesthetics in rabbits. There is a wide range of dosing reported. However, a general rule of thumb is to insert the needle cranially through the testicle’s caudal pole and inject until the testicle becomes turgid, keeping the total dose of lidocaine no higher than 2 mg/kg, although a total dose as high as 4 mg/ kg can be considered if needed (Guzman 2023). Considerations beyond pharmacological should be part of any pain management plan for rabbits. Positioning the surgery table so the

head is slightly elevated will help keep pressure off the diaphragm and reduce respiratory effort. Feeding as soon as possible in recovery will help avoid gastrointestinal complications. As mentioned, place rabbits in a quiet area away from other animals, especially potential predators, to allow the rabbit to exhibit natural behaviors, including pain behaviors.

11.5 ­Conclusion In all settings, regardless of how fast paced they are, it is imperative to meet the needs of our patients and provide adequate analgesia for surgical and medical conditions. Along with providing appropriate medications, staffing should be a consideration to allow for perioperative and medical treatment ­monitoring to address early signs of discomfort. By using a multimodal analgesic approach, enabling trained staff, and budgeting appropriately, we can ensure that adequate analgesia is never compromised even in resource limited settings.

­References Becker, L. (2022, July 29). Fear free pre-­visit and other drug charts. Fear Free Pets. https:// fearfreepets.com/fear_free_drug_charts (accessed March 6, 2023). Benato, L., Murrell, J., and Rooney, N. (2022). Bristol rabbit pain scale (BRPS): clinical utility, validity and reliability. BMC Veterinary Research https://doi.org/10.1186/s12917-­ 022-­03434-­x. Brown, C.R., Garrett, L.D., Gilles, W.K. et al. (2021). Spectrum of care: more than treatment options. Journal of the American Veterinary Medical Association 259 (7): 712–717. https://doi.org/10.2460/javma. 259.7.712. Carlson, A.R., Nixon, E., Jacob, M.E., and Messenger, K.M. (2020). Sterility and

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concentration of liposomal bupivacaine single-­use vial when used in a multiple-­dose manner. Veterinary Surgery 49 (4): 772–777. Chabot-­Doré, A.J., Schuster, D.J., Stone, L.S., and Wilcox, G.L. (2015). Analgesic synergy between opioid and α2-­adrenoceptors. British Journal of Pharmacology 172 (2): 388–402. https://doi. org/10.1111/bph.12695. Epub 2014 Jul 1. PMID: 24641506; PMCID: PMC4292955. Deflers, H. et al. (2022). Effects of a single opioid dose on gastrointestinal motility in rabbits (Oryctolagus cuniculus): comparisons among morphine, butorphanol, and tramadol. Veterinary Science 9 (28): https://doi.org/ 10.3390/vetsci90110028. Gowan, R.A., Baral, R.M., Lingard, A.E. et al. (2012). A retrospective analysis of the effects

 ­Reference

of meloxicam on the longevity of aged cats with and without overt chronic kidney disease. Journal of Feline Medicine and Surgery 14 (12): 876–881. https://doi.org/ 10.1177/1098612X12454418. Grubb, T. and Lobprise, H. (2020). Local and regional anaesthesia in dogs and cats: overview of concepts and drugs (part 1). Veterinary Medicine and Science 6 (2): 209–217. https://doi.org/10.1002/vms3.219. Grubb, T., Sager, J., Gaynor, J.S. et al. (2020). 2020 AAHA anesthesia and monitoring guidelines for dogs and cats*. Journal of the American Animal Hospital Association 56 (2): 59–82. https://doi.org/10.5326/jaaha-­ ms-­7055. Guzman, D.S.M. (2023). Pain Management. Veterinary Clinics of North America 23 (1): 187–218. Loix, S., De Kock, M., and Henin, P. (2011). The anti-­inflammatory effects of ketamine: state of

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the art. Acta Anaesthesiologica Belgica 62 (1): 47–58. PMID: 21612145. Miller, A.L. et al. (2022). Evaluating pain and analgesia effectiveness following routine castration in rabbits using behavior and facial expressions. Frontiers in Veterinary Science 9: 1–11. https://doi.org/10.3389/fvets.2022. 782486. Monteiro, B.P., Lascelles, B.D.X., Murrell, J. et al. (2023). 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. Journal of Small Animal Practice. 64 (4): 177–254. https://doi.org/10.1111/jsap.13566 Sparkes, A.H., Heiene, R., Lascelles, B.D. et al. (2010 Jul). ISFM and AAFP consensus guidelines: long-­term use of NSAIDs in cats. Journal of Feline Medicine and Surgery 12 (7): 521–538. https://doi. org/10.1016/j.jfms.2010.05.004. PMID: 20610311.

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289

12 Pain Management in Equids Molly Cripe Birt1, Rebecca Johnston2, Rachael Hall3, and Janel Holden3 1

Purdue University College of Veterinary Medicine, West Lafayette, Indiana, USA Moore Equine Veterinary Centre, Rocky View, Alberta, CA, Canada 3 Washington State University College of Veterinary Medicine, Pullman, Washington, USA 2

12.1 ­Introduction

12.2  ­Pain Assessment in Horses

Over the last decade, there have been significant advancements in the field of equine ­analgesia, marking a substantial improvement in equine clinical practice. Historically, the management of pain in horses fell short, with a prevailing inclination among equine clinicians to rely sparingly on analgesics, mainly due to concerns of potential adverse effects. Additionally, a ­conventional but outdated belief persisted that  minimizing analgesia was beneficial, as it  was  thought that completely relieving pain might encourage excessive movement in equids, potentially leading to self-­inflicted harm. However, it is now recognized that administering appropriate analgesia offers a multitude of benefits in equine care. Beyond alleviating discomfort, proper pain management plays a pivotal role in enhancing the recovery process, shortening healing times, stimulating appetite, improving the overall attitude and demeanor of the patient, and crucially, preventing the onset of dependent-­limb laminitis. These developments have transformed the approach to equid analgesia, ensuring the well-­being and welfare of these magnificent animals.

Pain in equids can manifest through alterations in their physiology, behavior, and emotional state. Some of these changes may be subtle. Chapter 4, Section 4.10 offers a detailed approach to assessing pain in equids.

12.3 ­Common Analgesics and Strategies in Horses Opioids can provide potent analgesia and are often used in combination with nonsteroidal anti-­inflammatory drugs (NSAID)s or alpha-­2 agonists to provide synergistic analgesia and sedation. The drugs most effective in the horse include butorphanol, morphine, methadone, meperidine, hydromorphone, fentanyl, and buprenorphine (Muir 2010). However, the use of opioids in the horse continues to remain somewhat controversial but appears to be largely dose and protocol dependent. It is believed that horses are quite sensitive to the central nervous system (CNS) stimulation caused by opioids (see Table 12.1) (Muir 2010). The CNS stimulation effects seem to be smaller

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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Table 12.1  Common non-­NSAID analgesics in the horse. Drug

Dosage range

Butorphanol

0.01–­0.02 mg/kg IV

Morphine

0.05–­0.3 mg/kg IV or IM

0.01–­0.02 mg/kg/h CRI 0.03–­0.1 mg/kg/h CRI Meperidine

1–­2 mg/kg IM 0.5–­1 mg/kg IV

Fentanyl

0.002–­0.005 mg/kg IV 0.005–­0.01 mg/kg/h CRI

Methadone

0.05–­0.2 mg/kg IV or IM

Buprenorphine

10–­20 μg/kg IV

Ketamine

2–­2.5 mg/kg IV loading dosage 0.5–­3 mg/kg/h CRI anesthesia adjunct 0.5–­1.5 mg/kg/h CRI standing analgesia

Lidocaine

1.3–­2 mg/kg IV loading dosage 3 mg/kg/h

Xylazine

0.5–­1.1 mg/kg IV 0.65 mg/kg/h

Detomidine

0.01–­0.04 mg/kg IV or IM 0.01–­0.02 μg/kg/min CRI 0.04 mg/kg PO (gel)

Romifidine

0.04–­0.12 mg/kg IV

Medetomidine

5–­20 μg/kg IV or IM 3.5 μg/kg/min CRI

Sources: Adapted from Clutton (2010), Yamashita and Muir (2009), Robertson and Sanchez (2010), Lerche and Muir (2009), Michou and Leece (2012a), Nann (2010), and Muir (2010).

in horses that have already received an alpha-­2 agonist sedative or acepromazine. CNS excitation also appears to be less or nonexistent in severely painful horses. Opioids are used to provide intraoperative analgesia to horses undergoing inhalational anesthesia. The ­anesthetic sparing effect of opioids is quite variable in horses in comparison to other species. Most studies have shown opioids to provide an  insignificant effect on mean alveolar

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concentrations (MAC), or even a MAC increasing effect, but these results vary greatly. Typically, the increase in MAC is due to the CNS stimulation from higher dosages of the opioid (Clutton  2010). Opioid constant rate infusion (CRI) efficacy in horses regarding MAC reduction is still being investigated but appears to be a reasonable option in certain cases of severe pain (Yamashita and Muir 2009). Studies have shown that the analgesia effects of opioids are best at low dosages or when opioids are used with nonopioid sedatives and sedative-­hypnotic drugs. There are concerns that intraoperative opioids can cause poorer recovery from general anesthesia either by prolonging recovery time or by causing an increase in locomotor activity  from the CNS effects. However, several reported clinical studies have indicated that morphine does not worsen recovery from general anesthesia (Clutton  2010) and might improve recovery when compared to recovery in horses not receiving opioids. Opioids can be used to enhance the analgesic and sedative effects of alpha-­2 agonists used during ­standing surgical procedures. The drugs most effective in this case include butorphanol, morphine, and methadone (Clutton  2010). Other opioids available for use in the horse include ­buprenorphine and meperidine (Michou and Leece 2012a). It is not uncommon, however, for opioids to be avoided in colicing horses because they can mask signs that would otherwise indicate the need for surgery in horses that do not yet have a definitive diagnosis (Mair 2008).

12.3.1 Butorphanol Butorphanol is an opioid agonist–­antagonist and provides good visceral anesthesia in the horse. This drug is recommended for controlling visceral (abdominal/colic) pain either as a bolus or as a CRI (Lerche and Muir 2009). Butorphanol is often used in combination with alpha-­2 agonists to provide synergistic sedation effects as well. Though severe pain of large colon torsion and small intestinal volvulus

12.3  ­Common Analgesics and Strategies in Horse

may not be controllable, a dosage range of approximately 0.01–­0.4 mg/kg can be given to control the pain of severe colic (Nann  2010; Bidwell 2009). The CRI dosage is 0.01–­0.02 mg/kg/h (Lerche and Muir 2009). The duration of action when given IV is approximately 45–­90 minutes (Bidwell 2009). Butorphanol is also used intraoperatively during exploratory laparotomy, at 0.02–­0.1 mg/kg IV every 30–­60 minutes and can also be administered as a CRI. While butorphanol does not directly cause inhalant MAC reduction, it does contribute to an overall smoother anesthetic period by controlling intraoperative pain (Trim and Moore  2007). Butorphanol has been shown to decrease pain scores in the horse and improve recovery and overall outcome compared to NSAID therapy alone stressing multimodal approaches like in other species (Robertson and Sanchez  2010). The potential negative side effects of butorphanol include ataxia, twitching/head jerking, and reduced motility of the small intestine. The cardiovascular system is not affected by butorphanol, and therefore it can be safely used as part of a premedication protocol for patients exhibiting circulatory shock.

12.3.2 Buprenorphine Buprenorphine, which is expensive for use in the horse, has limited information regarding analgesic efficacy when used; however, when administered with alpha-­2 agonists IV, this combination provides good postoperative analgesia. Buprenorphine can also be administered by oral transmucosal route, which produces the desired effect in 45 minutes and can last up to 12 hours (Michou and Leece 2012a).

12.3.3 Meperidine Meperidine is a synthetic weak mu opioid receptor with minimal adverse effects in the horse but provides minimal, short term, variable analgesia. Meperidine can potentially ­contribute to obstruction of the GI tract by reducing colonic

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motility when used repeatedly and has the potential to cause anaphylaxis in the horse when administered IV. Therefore, it should be given IM or SC (Trenholme et  al. 2020). Pain upon injection is reported and a large volume is typically required. This ­combined with a shorter duration of action compared with morphine make meperidine less likely to be recommended (Michou and Leece 2012a).

12.3.4 Tramadol Tramadol is an opioid receptor agonist, as well as a neuronal serotonin and norepinephrine reuptake antagonist. A study conducted on horses with chronic laminitis revealed that oral tramadol exhibited  only a short-­lived antinociceptive effect. Additionally, it had minimal impact on plasma tumor necrosis factor (TNF)-­a concentrations. The limited analgesic efficacy of tramadol in this context was not attributed to poor oral ­bioavailability but possibly the horse’s rapid ability to generate two primary tramadol metabolites, M1 and M2. M1 specifically undergoes rapid and extensive conjugation –­approximately 99%. Subsequent research in horses with chronic laminitis demonstrated a significant decrease in off-­loading frequency when a 10-­mg/kg dosage was used, but not with a 5 mg/ kg dosage. Tramadol does carry risks of gastrointestinal adverse effects, particularly at the 10 mg/kg dosage. One out of nine horses administered tramadol (10 mg/kg orally, every 12 hours for 5 days) experienced mild colic. Tramadol may have a role in managing laminitis pain. However, it might not be sufficient as a standalone treatment for chronic laminitis cases, despite its multimodal mechanisms of action. A combination of ketamine and tramadol could potentially be ­effective in addressing chronic laminitis pain (Guedes 2017).

12.3.5  Pure Opioid Agonists Morphine is a pure ­opioid agonist. The analgesic effects of morphine can last 4–­6 hours with a

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dosage range of 0.1–­0.2 mg/kg IV. When administered IV, however, it must be given slowly over about 5 minutes to avoid the potential for histamine release. In comparison to butorphanol, morphine is superior for superficial and deep somatic (musculoskeletal) pain and is also significantly less expensive. It is often administered in combination with an alpha-­2 agonist or a sedative–­hypnotic drug like acepromazine when used for standing surgical procedures or as a preanesthetic to avoid excitation in the awake horse. Morphine also has the potential to cause ileus and impactions; thus, the use of systemic morphine (and other opioids) remains controversial. There have been many studies performed to prove or disprove the theory that opioids cause post-­anesthetic colic (PAC), with varying results. Some studies showed a much higher risk of colic when using morphine ­versus butorphanol in horses undergoing orthopedic surgery. However, the dosages were inconsistent, so it is possible that severe orthopedic pain contributed to the development of PAC. Other potential causes of PAC include fasting the horses longer than 12 h for surgery, the stress response of the body when dealing with ­anesthesia/surgery, drugs used to decrease the stress response (­sedatives, phenothiazines), inhalant anesthetics, and NSAIDs (Clutton  2010). There has been no definitive proof of opioids being the direct or only cause of PAC. Pure­opioid agonists, though more potent, are not typically used to manage colic pain due to the increased negative GI side effects and the higher potential to cause excitement. However, in combination with an alpha-­2 agonist, excitement is decreased or nonexistent. This is also true when pure­ opioid agonists are used in severely painful horses (Table 12.2). Table 12.2  Various opioid affects. ●● ●● ●● ●● ●●

Increased locomotor activity Disorientation Ataxia Hyperresponsiveness to touch and sound Seizures (with very large dosages)

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Preservative-­free morphine can be administered for epidural analgesia as well as intra-­ articular analgesia. Epidural morphine can provide anywhere from 8 to 16 hours of analgesia at a dosage of 0.1 mg/kg, and CNS excitation is not seen (N.A. White, pers. comm.). When morphine is administered intra-­ articularly during orthopedic surgery, it seems to have long-­lasting results (Baller and Hendrickson 2002). Methadone has affinity for the N-­methyl-­D-­ aspartate (NMDA) receptors, which makes it useful when dealing with wind-­up pain and chronic pain. It can provide good analgesia in the horse for 4–­6 hours. Fentanyl is another great option in horses but must be administered as a CRI due to its  short half-­life. The peak effect occurs at approximately 5 minutes with duration of action of about 30 minutes. When used in the awake nonpainful horse, it can cause hyperresponsiveness and excitability. Fentanyl infusions that were designed to produce clinically significant analgesia caused only a minimal reduction in MAC and did not produce somatic or visceral analgesia. Fentanyl is also available as transdermal patches, which are designed to be time-­released at a specific amount of fentanyl per hour, which then has systemic uptake. As with other species, there are substantial variations in the plasma drug concentrations depending on the individual patient, changes in body temperature, and patch location (Lamont and Matthews  2007). Horses would require several patches to achieve the optimal dose making them a less practical method.

12.3.6  Non-­steroidal Anti-­inflammatories NSAIDs are typically the initial agent used to address inflammatory pain and clinical signs of endotoxemia, associated with ischemia or damage to the intestinal barrier (Table 12.3). Flunixin meglumine and ketoprofen are most effective against endotoxemia (Trim and Moore  2007). Flunixin is the most common NSAID used when treating colic pain. Flunixin (1.1 mg/kg IV SID

12.3  ­Common Analgesics and Strategies in Horse

Table 12.3  Dosages for NSAIDs. Drug

Dosage

Duration

Flunixin meglumine

0.25–­1.1 mg/kg IV or PO

6–­12 h

Phenylbutazone

2.2–­4.4 (up to 6) mg/kg IV or PO

Up to 14 h 6–­24 h

Ketoprofen

2.2–­3.6 mg/kg IV or IM

Diclofenac (1%)

5 in. strip of cream applied over affected joints

Firocoxib

0.3 mg/kg PO loading dosage then 0.1 mg/kg PO; 0.09 mg/kg IV

24 h for PO 24 h for IV

Meloxicam

0.6 mg/kg IV or PO

12–­24 h

Carprofen

0.7 mg/kg IV or 1.4 mg/kg PO

24 h for PO/IV

Vedaprofen

2 mg/kg PO and then 1 mg/kg PO

12 h

Source: (Davis 2009), (Driessen et al. 2010), (van Weeren 2010), (Michou and Leece 2012b).

for up to 5 days) is effective against endotoxemia for 6–­8 hours and provides pain relief for up to 12 hours (Doherty 2022). If pain does not subside after receiving flunixin, or returns soon after, it should be assumed that the horse has a more significant disease process and needs further treatment, including other analgesics with a different mechanism of action.

12.3.7  NMDA Receptor Antagonists Ketamine is considered a dissociative anesthetic and is often used as an induction agent for horses in combination with a benzodiazepine and/or alpha-­2 agonist. By antagonizing the NMDA receptor, a cataleptic state, amnesia, and analgesia are achieved. Ketamine is used in a variety of drug combinations to induce anesthesia, provide total intravenous anesthesia, and as an adjunct for analgesia. When ketamine is used to aid in analgesia, the dosage is much lower than the dosage needed for anesthesia induction. It is often used intraoperatively as an adjunct to inhalant anesthetics along with opioids, alpha-­2 agonists, and local anesthetics to provide analgesia and decrease MAC. When used as an adjunct, as a CRI, there is an obvious reduction in MAC as well as an increase in cardiac output at ­subanesthetic dosages (Yamashita and Muir 2009). Partial intravenous anesthesia infusion

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techniques can be used during inhalant anesthesia, which can reduce the inhalant requirement by almost half. These infusions can also improve cardiac function and recovery scores (Yamashita and Muir 2009). Studies performed to test the efficacy of low-­dosage ketamine infusions for analgesic purposes showed little effect in horses suffering from painful conditions such as colic and osteomyelitis, suggesting that low-­dosage ketamine infusions are best used in conjunction with other analgesics (Driessen et al. 2010). Ketamine is often infused at a rate of 0.5–­3 mg/kg/h. If procedures are going to last longer than 1.5–­2 hours, it is ­recommended that the ketamine rate not exceed 1 mg/kg/h because of the negative excitatory effects seen in recovery (Bettschart-­ wolfensberger and Larenza 2007).

12.3.8  Alpha-­2 Agonists Alpha-­2 Agonists are often used to sedate the horse to facilitate a full physical exam including a rectal examination and nasogastric intubation. They also provide good visceral analgesia. Xylazine, detomidine, and romifidine are the most described in the literature and commonly used in the equine practice (Moens et al. 2003). Depending on dosage the sedation lasts approximately for 20–­30 minutes and visceral analgesia can last up to 90 minutes (Robertson and

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Sanchez  2010; Sanchez and Robertson  2014). This duration of time is sufficient to perform the exam and to evaluate the effectiveness of the analgesia. The dose-­dependent duration of action is a bit longer than xylazine, up to 60–­120 minutes. The benefit of romifidine is that the horse experiences less ataxia compared to the other alpha-­2 Agonists. Butorphanol is often used in combination with an alpha-­2 agonist during the initial colic exam as well as part of the preanesthetic sedation prior to surgery.

12.3.9  N-­butylscopolammonium Bromide (NBB) NBB possesses both anticholinergic and antispasmodic properties, albeit for a relatively brief duration of approximately 15–­20 minutes. The drug is a preferred option for treating nonstrangulating obstructions of the large colon, including cases of spasmodic colic. The administration of NBB also leads to a reduction in rectal tone, making rectal examinations more manageable. However, it’s important to exercise caution when administering NBB, either on its own or in conjunction with xylazine, as it can induce tachycardia and affect blood pressure, which warrants consideration when using NBB in animals with preexisting systemic compromise or moderate to severe tachycardia (Sanchez and Robertson 2014).

12.3.11  Prokinetics and Antispasmodics Drugs that promote normal GI activity, such as prokinetic agents and spasmolytics, can provide indirect analgesic effects. The prokinetics available include metoclopramide (for emptying the stomach), neostigmine, cisapride, bethanecol, and erythromycin (Mair 2008). Metoclopramide administered as a CRI (0.04 mg/kg/h) will restore coordinated gastroduodenal activity and transit of ingesta (Koenig and Cote  2006). There are reports of sweating, excitement, and restlessness with metoclopramide administration. Cisapride is noted to have similar prokinetic benefits without the side effects of metoclopramide. Intestinal spasms/contractions are painful. Antispasmolytic drugs that are cholinergic blockers can help reduce these spasms. Atropine can relax the wall of the intestine in cases of spasmodic colic, but it can also cause ileus and tympany. Therefore, the use of atropine in the treatment of colic is not recommended. Buscopan® is a combination of an NSAID (dipyrone) and a cholinergic agent (hyoscine). Buscopan decreases GI spasms by inhibiting parasympathetic effects on smooth muscle. It is often used for spasmodic episodes and gas colic, as well as mild impactions (Bidwell  2009). Buscopan® can also be used to relax the walls of the rectum to facilitate a thorough rectal exam in a tense horse and will cause a transient tachycardia.

12.3.10  Dimethylsulfoxide (DMSO) DMSO is a controversial drug that was first used as an industrial solvent. However, multiple studies have shown its utility for painful conditions in horses such as tendonitis, ­laminitis, synovitis, and cutaneous pythiosis, among others. Topic gels are the most common route of administration, but intravenous and intra-­articular use has also been described. Use of DMSO has largely fallen out of favor in the United States (Douwes and Kolk 1998; Sotelo et al. 2020; Atiba et al. 2020).

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12.3.12  Locoregional Anesthetics and Techniques Local anesthetics are widely used in equine practice, aiding in lameness localization, standing surgical procedures, orthopedic surgery, castrations, ocular exams/procedures, dental procedures, wound management, and as an adjunct to inhalant anesthesia. The drugs can be administered at specific sites (local blocks), infiltrating around innervated areas (regional blocks), and applied topically. The

12.4  ­Lidocaine Use in Horse

most common local anesthetics used in equine clinical practice are mepivacaine, bupivacaine, ropivacaine, and lidocaine. Mepivacaine is most often used during lameness exams as a joint or nerve block to aid in lameness localization due to its rapid onset and favorable duration of action (1–­3 hours). It is also used for local blocks during short-­ standing surgical procedures and intratesticular blocks for castrations (Abass et al. 2018). Lidocaine can be used for local nerve blocks, epidurals, as intravenous infusions for analgesia and MAC reduction under anesthesia, a prokinetic agent for GI disease, and to treat ventricular arrhythmias (Freeman  2019). Lidocaine can also be administered rectally via a syringe (35 ml of 2% lidocaine for a 450 kg horse) to facilitate rectal exams if the horse is not relaxing enough or there is a higher risk of rectal tear. This can be used in absence of Buscupan™ or can be used simultaneously. Chapter  6, Section  6.7  has equine-­specific blocks as well as general descriptions of various blocking techniques that can be used in equid patients.

12.4  ­Lidocaine Use in Horses One of the major challenges of horses under general anesthesia is the hypotension that occurs not only in emergency colic surgeries but also in healthy horses undergoing elective surgeries. Inhaled anesthetics are one of the major contributors. One of the ways to reduce the amount of inhalant delivered to the patient is to add additional analgesic agents that help decrease the minimum alveolar concentration MAC. There are several ways to accomplish this goal, depending on the surgery. Analgesia CRIs and local and regional blocks are all excellent ways of providing additional analgesia and reducing MAC. In horses, the administration of lidocaine through intravenous infusions has been found to reduce inflammatory responses during

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episodes of intestinal ischemia and reperfusion. Although lidocaine does not seem to affect the normal transit time of gastrointestinal processes, it has been shown to decrease the occurrence of reflux associated with ileus (Malone et al. 2006). When it comes to the visceral mechanical nociception of a healthy equine duodenum, intravenous lidocaine does  not appear to have a significant impact. However, it’s important to note that its effects on injured or inflamed viscera have not been thoroughly assessed (Guedes 2017). One of the most common uses is with a 2% lidocaine CRI running at 50 mcg/kg/min with a 1 mg/kg ­loading dosage during anesthetic procedures. Lidocaine not only reduces MAC, but it also  decreases postoperative pain (Koppert et  al.  2004). After induction, once can expect ~25% reduction in isoflurane vaporizer settings after administering a 2.5 mg/kg bolus over 10 minutes followed by a CRI at 50 mcg/kg/ min (Dzikiti et al. 2003). There have been conflicting findings regarding the thermal antinociception produced by intravenous lidocaine, either alone or in combination with ketamine and/or butorphanol. In contrast, this approach has been effective in  reducing postsurgical abdominal pain in humans (Guedes 2017). Providing local anesthesia for horses undergoing castration is increasing in popularity. This is accomplished by injecting the spermatic cord and/or testes with a local anesthetic (Skarda et  al.  2009). The testicular and spermatic cord blocks will decrease the systemic pain management requirement of horses undergoing castration, which allows for a lower rate of inhalant or injectable anesthetic if a field procedure is performed.

12.4.1  Postoperative Period Lidocaine Use One of the main concerns of anesthetizing equines is the recovery period. It is recommended that lidocaine CRIs be discontinued

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thirty minutes before moving to recovery. Ataxia and overall poor recoveries were noted when the lidocaine CRI was discontinued at  the end of surgery (Gozalo-­Marcilla et  al.  2014). Lidocaine has proven to be very useful when administered systemically for the treatment of postoperative pain associated with ileus and reperfusion injury, and the treatment of systemic inflammatory response syndrome (SIRS) associated with reperfusion injury and inflammatory diseases of the bowel. Studies have found that lidocaine will reduce circulating catecholamines and decrease inflammation by the inhibition of prostaglandins, granulocytic migration, cytokine release, and free radical production (Smith and Pusterla 2021). The clinical signs of lidocaine toxicity include ataxia, muscle fasciculations, excessive blinking, nystagmus, and recumbency. In extreme cases, seizures and coma are possible.

12.5 ­Common Painful Conditions and Procedures in Horses 12.5.1  Surgical Pain Preemptive or preoperative analgesia should be initiated to prevent the start of central sensitization and wind-­up pain. NSAIDs, alpha-­2 agonists, opioids, and local anesthetics can be used in the preoperative period. Use of these drugs preemptively can reduce intraoperative analgesic dosages and inhalant requirements. Flunixin meglumine (1.1 mg/kg) is commonly used for expected visceral and soft tissue pain, while phenylbutazone (2.2 mg/kg) remains the preferred NSAID for expected orthopedic pain. The combination of an alpha-­2 agonist and opioid will aid in a smooth induction of the patient and provide the added benefit of analgesics. Regional and local anesthesia is necessary in standing surgical procedures, as sedation and preoperative NSAID use is not sufficient for both preventing pain in a semiconscious animal and providing safety for the surgical team.

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Regional and local anesthesia includes epidurals, line blocks, distal limb perineural anesthesia, paravertebral blocks, and blocks of facial nerves such as the maxillary block. The use of locoregional blocks in anesthetized patients will reduce the need for intraoperative ­administration of opioids, decrease MAC of inhalant anesthetics and improve patient recovery scores (Goodrich 2009; Creighton and Lamot 2022). Intraoperatively, strategies aimed at controlling pain include opioid boluses or CRIs, lidocaine CRIs, and ketamine CRIs, which can and often are continued at decrease dosing during recovery and the postoperative period. Alpha-­2 agonists are used to sedate the horse to prolong lateral recumbency to allow the horse time to metabolize the anesthetics and return to consciousness without panicking and attempting to stand too soon. Horses have a strong flight response and do not stay recumbent for any length of time. Often their brain will “wake up” before the rest of their body does. Attempts to stand prior to full consciousness can result in injuries that can include fatal limb fractures. Providing analgesia in the recovery period will allow the horse to return to full consciousness in a much calmer fashion, with more coordinated attempts to stand. The use of an opioid, such as morphine, can provide analgesia well into the recovery period. Intraoperative morphine has been shown to improve recoveries by decreasing overall recovery time and decreasing attempts to stand (Lerche and Muir 2009) (Figures 12.1 and 12.2).

12.5.2 Gastrointestinal (Colic and Ulcers) Pain Acute abdominal pain, or colic, is the most common emergency in the horse necessitating immediate pain relief. Referred pain from hepatic, respiratory, muscular, or genitourinary diseases can cause colic signs and must be considered until a definitive diagnosis is made (Smith and Pusterla 2021). Pain resulting from disease or abnormality of the gastrointestinal tract include distension of the intestine from

12.5  ­Common Painful Conditions and Procedures in Horse

Figure 12.1  A maxillary nerve block is placed above the zygomatic arch using a 20-gauge x 3.5" spinal needle and 10 - 15 ml of mepivacaine for a dental extraction of the upper arcade. Source: Courtesy of Molly Cripe Birt.

bowel, ischemia of the bowel, and pulling on the root of the mesentery. Initial goals of analgesic therapy are to provide pain relief for the horse and ensure safety while a thorough colic work-­up examination is performed. Analgesia can provide temporary relief from gas distension and decreased inflammation; however, care must be taken to avoid masking the signs of surgical pain. Therefore, sedation using alpha-­2 agonist is recommended for the safety of the patient, client, and staff during the workup. Xylazine (0.3–­1.0 mg/kg) is a popular sedation, as sedative effect will last approximately 20 minutes, allowing for safe handling as well as temporary relief of pain that does not mask surgical pain (Doherty  2022). Decompression via nasogastric intubation of the distended stomach or loop(s) of intestine can provide temporary pain relief until a definitive diagnosis is made.

12.5.3 Lameness

Figure 12.2  Utilization of intravenous and intramuscular sedation (combination of alpha-2 agonist and opioid), non-steroidal antiinflammatory drug, and a local anesthetic block makes standing surgery of the inter-spinous ligament desmotomy (Kissing Spine Surgery) possible. Source: Courtesy of Molly Cripe Birt.

gas, ingesta or foreign body impaction within the bowel lumen, inflammation of the GI tract, bowel displacement, torsion or volvulus of

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Pain of musculoskeletal structures causes pain that can be described as acute or chronic. Acute lameness is a sudden onset of pain, and often fracture, synovitis, penetrative wounds, subsolar abscess, and acute laminitis will be considered on the differential list. Chronic lameness is unrelenting pain that is experienced over a long period of time. Osteoarthritis and chronic laminitis are the most common sources of chronic pain. Diagnostics for lameness cases include a passive and active lameness examination, application of hoof testers, synovial fluid analysis, blood chemistries, ultrasound examination and radiographs. In some instances, advanced imaging diagnostics using computed tomography, magnetic resonance imaging and nuclear scintigraphy might be considered on a case-­by-­case basis. 12.5.3.1  Acute Lameness

Treatment of acute lameness should begin with immediate stabilization and support of  the affected limb and immobilization of the  patient. Pain control should begin by

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decreasing inflammation with NSAIDs. If a fracture is suspected, external coaptation must be placed and the patient kept calm to reduce further injury. Jogging a horse for a lameness examination is contraindicated in patients with suspected fractures. Horses typically require sedation for diagnostics, although heavy sedation is contraindicated in suspected fractures, as ataxia can result in further injury of the fracture. The use of an alpha-­2 agonist for sedation will provide some analgesia. Once a diagnosis is made, a treatment plan can be formulated for each specific case. The NSAID phenylbutazone is most often used to treat musculoskeletal inflammatory pain (Porter 2009). Meloxicam (0.6 mg/kg IV or PO SID) has been found to be effective, but it is not labeled for use in equids in the United States (Ursini  2022). Other systemic analgesics and, when possible, regional and local anesthetics are recommended. 12.5.3.2  Chronic Lameness

The most common causes of chronic pain in the horse include osteoarthritis, navicular ­syndrome, tendinopathy, and laminitis (founder). Management of pain associated with musculoskeletal disease begins at NSAID administration, with phenylbutazone remaining the most popular. Firocoxib was recently approved for use in horses suffering from osteoarthritic pain (Fadel and Giorgi  2023). Studies report that firocoxib (0.1 mg/kg PO SID) is effective for clinical improvement, and as a COX-­2 selective NSAID will have less negative gastrointestinal complications (Ursini 2022).

12.5.4 Osteoarthritis Osteoarthritis is the chronic, degenerative degradation of the cartilage and bony surface of joints. It is typically caused by repetitive mechanical stress on the joint, which can occur from continued micro-­traumas, such as daily athletic use. Osteoarthritis can  also

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develop secondarily to traumatic injury, including surgery, or septic synovitis (Mcllwraith  2011). Navicular disease is the degenerative change of the distal sesamoid (navicular) bone, resulting in damage to ­cartilage, bone, and the deep digital flexor tendon. Both primary osteoarthritis and navicular syndrome develop in horses with increased risk factors, such as age and occupation. Therefore, there are many strategies to limit the progression of these diseases and preserve the integrity of the related synovial structures. This includes proper training and performance plans, nutrition, husbandry (standing mats), and corrective shoeing. Combined or separate intra-­articular injections of a corticosteroid and hyaluronic acid have been used preemptively and palliatively in horses diagnosed with osteoarthritis and navicular syndrome. Retrospective studies are analyzing the efficacy of these practices; ­however, they remain popular in sports medicine practices. Methylprednisolone acetate (Depo-­Medrol), triamcinolone acetonide and bethamethasone esters have all been ­utilized. Reducing the inflammatory cell infiltration of the joint synovium slows the degradation of joint structures, thus maintaining joint function (Mcllwraith  2011). Triamcinolone has chondroprotective properties, making it an ideal corticosteroid for use in high-­motion joints. Paired with an appropriate corticosteroid are intra-­articular injections of compounds such as hyaluronic acid. Hyaluronic acid has anti-­inflammatory effects, as it has a protective response against inflammatory mediators. Due to the potential complication of laminitis ­associated with steroid administration, it is ­recommended that clinicians not exceed 45 mg of triamcinolone for a maximum dose (Mcllwraith  2011). Corticosteroid injections into lesions of the tendon or ligament will be catastrophic for repair and are contraindicated. Regenerative medicine has grown in popularity with positive anecdotal reports for osteoarthritis in the horse, but further clinical

12.5  ­Common Painful Conditions and Procedures in Horse

trials must be completed to identify the action and the best methods of processing auto-­ biologically derived therapies. Applying regenerative medicine on a case-­by-­case basis may aid in the healing of the degenerative injury, even if in its acute phase, which may mitigate the development of chronic pain. Autologous conditioned serum (ACS) is a processed blood product that concentrates the anti-­inflammatory protein interleukin-­1 antagonist protein. With intra-­articular injections, ACS has been reported to have decreased synovial hyperplasia, less cartilage fibrillation, and less synovial hemorrhage (Mcllwraith  2016). Bone marrow harvested from the sternum or tuber coxae yields the most mesenchymal stem cells (MSCs), which are then centrifuged on-­ site or cultured for expansion in a laboratory. Some studies report that MSCs will decrease progression of osteoarthritis, as well as ­positively contribute to the natural repair of tendon fibers (Mcllwraith  2011; Geburek et al. 2016). Platelet-­rich plasma (PRP) is a volume of plasma with concentrated platelets higher than that of whole blood, often processed on-­site. These concentrated platelets will enhance tenocyte proliferation and the collagen matrix synthesis, thus decreasing clinical signs of lameness (Ortved 2018). Other pharmacologic methods can be used to slow the degenerative process of osteoarthritis and navicular syndrome, which thereby reduces pain. Routine intramuscular injection of polysufated glygosaminoglycans (PSGAG) (Adequan®) will increase collagen and glycosaminoglycan synthesis. Pentosan polysulfate (Zycosan®) is a plant-­based heparinoid compound that is found to decrease cartilage fibrillation and reduction in lameness scores. Joint supplements, also referred to as nutraceuticals, are popular in practice but have little more than empirical evidence supporting prevention or further degradation of joint cartilage. Human and animal meta-­analysis studies show little to any benefit of most joint supplements on the market.

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12.5.5 Laminitis Laminitis is the inflammation of the sensitive laminae within the hoof capsule, and it is a debilitating pain regardless of it being acute or chronic in origin. Horses suffering from both acute and chronic laminitis will require treatment of the inciting cause to prevent progression of the disease and pain. Laminitis is a very complex syndrome that can cause extreme suffering if treatment is not implemented early. Laminitis is considered neuropathic pain, which can be very hard to treat (Figure 12.3). Acute onset of laminitis can occur in the form of support-­limb laminitis. This happens when there is excessive weight-­bearing on one limb due to severe lameness on the contralateral limb. It is common in horses with fractures and septic joints, as they bear weight predominantly on the opposing limb to avoid pain associated with the inciting injury. Acute laminitis is a complication of endotoxic diseases, such as strangulating GI obstruction, enterocolitis, anterior enteritis, retained placentas, metritis, grain overload, and pleuropneumonia (Eades et al. 2002). Laminitis is a common sequela of metabolic diseases, and painful episodes will flare when the metabolic condition is not ­controlled. Treating the inciting disease will

Figure 12.3  Acute onset of laminitis in a post-operative resection anastamosis patient with a history of Equine Metabolic Syndrome. Note use of Soft Ride orthotic boots and use of ice boots for cryotherapy. Source: Courtesy of Molly Cripe Birt.

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reduce the progression of laminitis. Without proper treatment, the acute phase of laminitis will cause wind-­up pain that can easily proceed to chronic pain. For more information on the progression of acute pain to chronic pain, please see Chapter 4. The use of cryotherapy remains a popular application for laminitis prevention and treatment. Many cases of laminitis need supportive or corrective horseshoeing. Horses suffering from both acute and chronic laminitis must have pharmacological intervention, and treating the inciting disease will reduce the progression of laminitis. Aggressive treatment with NSAIDs is necessary to inhibit the inflammatory cascade and resulting nociceptive and neuropathic pain. Most studies show that phenylbutazone has the most potent effect on ­laminitis pain (Driessen et al. 2010). Phenylbutazone remains a superior, and therefore more popular, NSAID when treating the pain of laminitis. However, flunixin meglumine is used most often to combat SIRS, which contributes to the progression of laminitis. DMSO is a free radical scavenger and has been administered in cases where ischemia and reperfusion injury result in acute laminitis. The systemic side effects of high dosages of NSAIDs for the long term must be considered and prevented if possible. Omeprazole and/or sucralfate can be used to protect the stomach after NSAID administration; however, misoprostol has been found to be superior to the use of omeprazole and sucralfate in combination (Figure 12.4) (Varley et al. 2019). Lidocaine delivered as a constant-­rate infusion can be effective in treating chronic laminitis because the sensory nerves that innervate the foot have been shown to have histopathologic changes associated with neuropathic pain. Lidocaine also suppresses peripheral hyperalgesia, central sensitization, and allodynia. The use of locoregional analgesia and epidural analgesia is an effective component of multi-­modal pain management in chronic pain cases. Gabapentin (5–­20 mg/kg two to three times daily) can be adjunctly prescribed as part of a multi-­modal pain management

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Figure 12.4  A 2% Lidocaine (240 ml/hr) is delivered intravenously at a constant rate infusion to a patient with post-operative repair of a second phalanx fracture developing contralateral limb laminitis. Source: Courtesy of Emily Higdon.

plan to address the neuropathic pain (Gold et al. 2022; Hopster and Eps 2019). Other considerations include constant rate infusions of lidocaine or ketamine, intramuscular injections or constant rate infusions of butorphanol or morphine, and transdermal patches of fentanyl (Hopster and Eps 2019).

12.5.6 Pleuropneumonia Initial diagnosis involves a thoracocentesis to obtain a fluid sample for analysis as well as therapeutic evacuation of the pleural fluid. Often a chest tube is placed to allow drainage of further fluid accumulation as well as to perform therapeutic lavages of the pleural space. These procedures are done in the standing horse; sedation may not be necessary if the horse is very depressed, but analgesia is required as the procedures are incredibly painful. However, alpha-­2 agonists can be administered if necessary. Local or intercostal blocks can be performed prior to performing a thoracentesis and chest tube placement. A line/­ incision block can be done as well as intercostal blocks. NSAIDS are used to treat inflammatory pain and possibly reduce the production of

12.5  ­Common Painful Conditions and Procedures in Horse

pleural fluid by addressing the inflammation. Opioids such as butorphanol may need to be added for horses with intractable pain. This can be administered as IV boluses at a dosage of 0.05–­0.1 mg/kg or as a CRI. A loading dosage of 0.02 mg/kg IV, is recommended followed by a CRI of 0.013–­0.02 mg/kg/h. Hospitalization is often necessary for intravenous catheter placement and long-­term intravenous antibiotic therapy, so providing an analgesic CRI would be convenient and appropriate. If the horse does not respond to aggressive antibiotic therapy within the first 7–­10 days, fibrin and lung abscesses can develop, which could require surgical intervention. A thoracotomy is performed to evacuate fibrin from an abscess; ultrasonography should be performed to determine the abscess is completely walled off to prevent pneumothorax. The attending team should be ­prepared for pneumothorax regardless. If  abscessation and fibrin development is advanced, the surgeon might perform a rib resection with the thoracotomy. Locoregional anesthetic blocks using 2% lidocaine are necessary for these surgical procedures, and the use of pre-­ and postoperative NSAIDs must be utilized. Because patients with pleuropneumonia often develop SIRS, the anti-­endotoxemic effects of flunixin ­meglumine are warranted, as are preventative therapies such as cryotherapy of the hooves to decrease the development of laminitis (Figure 12.5).

12.5.7 Dystocia Dystocia –­difficult labor –­is a life-­threatening emergency for both the dam and the fetus. Advanced planning including a written standard operating protocol is very important for a successful outcome. In all dystocia patients, treatment proceeds on the assumption that the foal is alive, even if presumed dead (Bidwell 2013). Whatever happens to the dam happens to the fetus. This includes ventilation, perfusion, blood pressure changes, septicemia, stress, and the effects of most drugs. The fetus is already stressed; therefore, the drug protocol must be very carefully selected.

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Figure 12.5  A thoracotomy with a rib resection performed in a patient with severe pleuropneumonia causing abscessation of a portion of the lung and a fistula into the bronchus. Intercostal blocks should be utilized for this technique 2-3 ribs before and after the anticipated surgical site. Source: Courtesy of Carolyn McLaughlin.

Cardiopulmonary side effects of drugs administered to the dam can negatively impact the fetus; therefore, drugs with a shorter duration of action are preferable. Upon presentation, the mare will have a vaginal palpation performed and attempted assisted vaginal delivery. For the examination, these mares require sedation, often at a higher dosage due to extreme stress and excitation (A. Smith, pres. comm.). Xylazine dosage is 0.2 to 1 mg/kg IV, depending on the level of excitement of the mare (Bidwell 2013). Opioids and NSAIDs are typically avoided until after fetal delivery. If the mare must be anesthetized for controlled vaginal delivery and/or cesarean section, the analgesia selected, and anesthetic plan should be like that used for colic patients. Again, the veterinary team must consider that sedatives, tranquilizers, and opioids may ­further depress the fetus. Once the foal is

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delivered, more analgesics can be administered. Butorphanol can be given at 0.01–­0.08 mg/kg IV every 30–­50 minutes or as a CRI at 0.01–­0.02 mg/ kg/h (Bidwell  2013). Other analgesics options include morphine at 0.1 mg/kg IV bolus and/or morphine CRI at 0.1 mg/kg/h. A lidocaine CRI is appropriate for analgesia and MAC reduction with standard dosages. A ketamine CRI can also be administered, if necessary, with a loading dosage of 0.2–­0.4 mg/kg IV if the CRI is started thirty minutes or more past induction. The ketamine CRI dosage is 1–­2 mg/kg/h IV. All CRIs should be stopped 20–­30 minutes before the end of surgery to decrease the risk of ataxia in recovery (Figure 12.6). Uterine torsion is a dangerous reproductive emergency, often presenting with colic signs such as flank watching, pawing, kicking, and rolling. Several methods are used to attempt to correct the torsion. Sedation should be avoided with standing procedures, including manual manipulation via the vaginal canal, as second-­stage labor may occur immediately after correction. Epidural anesthesia can be

Figure 12.6  Controlled vaginal delivery in a mare with a dystocia. Source: Courtesy of Molly Cripe Birt.

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performed to decrease the amount of straining in these standing procedures. If manual manipulation is not successful, the mare may need to be anesthetized to attempt correction via rolling the mare over. Standard premedication and induction dosages for a dystocia can be used. Surgical intervention can also be performed as a standing procedure through a flank incision. A standing sedation protocol will be required, with the minimal amount needed to achieve chemical restraint. An epidural and local anesthetic should be used in this case as well.

12.6  ­Analgesia in Foals Analgesia in foals is still a subject with relatively few published studies on pain assessment and analgesic therapies. There are many studies in neonatal laboratory animals and human neonates assessing their experience of pain and suffering within the first weeks of life when neurologic development is still occurring. These studies show that all neonates who were exposed to painful stimuli with no analgesia experienced permanent changes such as decreased pain threshold and behavioral changes. With any species, it should be assumed that neonates will experience similar effects. In veterinary hospital settings foals can experience pain for several reasons including diagnostic sample collection, venipuncture, intravenous catheter placement, and nasogastric tube placement. Medical conditions that are painful to the foal can include colic, traumatic wounds or fractures, meconium impaction, gastric ulcers, enteritis, septic joints, uroperitoneum, large umbilical hernias, and flexural limb deformities. Foals with acute abdominal pain and severe lameness may exhibit obvious pain signs like adult horses. If a syndrome or procedure is painful to an adult horse, it can be assumed that it will be painful to the neonate and should be treated accordingly (Robertson 2012). Assessing subtle pain in foals can be difficult. A foal may only exhibit a mild change in

12.6  ­Analgesia in Foal

behavior that differs from its normal behavior. Therefore, observational reports from the ­caregiver/owner are imperative as a first line of assessment. Video monitoring while in the barn may also prove helpful by not having the observer influence behaviors when they are present. If the dam is present, the foal should remain with her for observation, evaluation, and treatment to promote the most normal behaviors possible. Some recent studies have been focusing on developing a facial expression-­based pain scale for equine neonates. The scale focuses on assessment of facial action units: head, eyelids, focus, corners of the mouth, muscle tone, smacking of the lips and ears (Lanci et al. 2022). There is limited information regarding pharmacokinetics or pharmacodynamics of most drugs in foals. Often the use of certain drugs has been extrapolated from their use in adults, which makes choosing analgesic drugs and determining accurate dosing more difficult to prevent drug toxicities in patients of this small size with underdeveloped metabolic pathways. Weighing of the foal and readjusting drug dosages is imperative over the course of treatment as foals on average gain 1.15 + − 0.17 kg/d (1.5–­3.3 lb/d). Foals under 2 weeks old have incomplete hepatic metabolism; therefore, drugs that require primary hepatic metabolism should be used with caution (Loberg 2010). These include opioids, benzodiazepines, ketamine, alpha-­2 agonists, and lidocaine. The negative side effects of drugs will be increased in the neonatal foal in comparison to adults (Bidwell 2013). Renal excretory function does not mature for 7–­10 days, making nephrotoxicity more likely in this developmental state. Dehydrated or compromised foals should be treated with caution, as there can be an increased incidence of toxicity. Prematurity may also affect the foal’s ability to metabolize and excrete medications. Foals have high extracellular fluid volume compared to adults, which can affect water-­soluble medications by requiring a higher dosage to reach the plasma and tissue concentrations of adults. Foals have lower serum total protein

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than adult horses. Medications that are protein bound, such as phenylbutazone, in foals may have the same serum concentration as adult horses; however, due to decreased protein binding free or active drug in the body may be higher in foals. In severe hypoproteinemia lower dosages may be required. Butorphanol is often used as the analgesic and sedative of choice in foals. Foals respond to this drug differently than adults and do not have increased locomotor activity or excitement (Robertson  2012). Drug clearance and uptake of butorphanol in foals is higher than adults and therefore higher dosages are required to produce analgesia. For foals up to 8 weeks old, 0.1 mg/kg IV is used. There have been no published studies regarding systemic efficacy or pharmacokinetics of morphine or fentanyl in foals; however, there is some pharmacokinetic data on transdermal fentanyl with results yielding variable peak plasma concentrations over time. Intra-­articular morphine to treat pain associated with infective synovitis or septic arthritis in foals is possible; further studies are needed to emphasize this (Robertson 2012). NSAIDs used in the foal include phenylbutazone, flunixin meglumine, ibuprofen, and ketoprofen. When using NSAIDs as analgesics, higher dosages may be required to achieve therapeutic plasma levels. If higher dosages are used, the interval between doses should be longer (Robertson  2012). NSAIDs should be used very cautiously in compromised foals; this includes dehydrated and/or hypovolemic foals as well  as those with renal compromise (Robertson 2012). Butorphanol may be a better option in these compromised patients. Intraoperative pain is an important concern for the anesthetist. Foals can appear adequately anesthetized but still respond quite unexpectedly to the initial surgical incision and other painful events during ­surgery. Butorphanol is the most common analgesic used for intraoperative pain. NSAIDs are also an option in healthy foals. Gastroprotectants are recommended when using NSAIDs, as studies have shown foals to have prevalence for developing

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gastric ulcers. Most commonly, a proton-­pump inhibitor like omeprazole (4 mg/kg PO SID) and/or sucralfate (20 mg/kg PO q 6–­8 hours) are utilized in foals  –­ misoprostol may also be useful. Local anesthetics such as nerve blocks and epidurals are possible. Foals can respond to pain more abruptly and vigorously than adults; therefore, providing a nociception blockade with locoregional analgesia can be beneficial. These are relatively simple procedures and have the added benefit of limited side effects and decreased need for systemic analgesics. Using lidocaine creams or gels for procedures such as venipuncture, IV catheter placement, oxygen cannula placement, and nasogastric tube placement can be ­beneficial. However, these products can take up to 30 minutes to reach peak efficacy. A simple bleb of lidocaine under the skin for venipuncture and IV catheter placement can be utilized when ­time is pressing. Alpha-­2 agonists can provide significant sedation and analgesia but are often avoided in foals under 1 month of age due to the profound cardiovascular side effects (Loberg  2010). Xylazine and romifidine produce less cardiopulmonary effects than detomidine and are good choices in healthy foals. The alpha-­2s can also be combined with butorphanol to provide more reliable sedation (Robertson 2012). The use of systemic lidocaine in neonates is somewhat controversial, despite the many benefits already seen in adult equines. As maximum dosages of systemic lidocaine in foals have not been established, lower dosages are recommended (Robertson  2012). Lidocaine is highly protein bound, so an excess of free drug may occur in the foal. Flunixin meglumine and ceftiofur sodium (antibiotic) decrease lidocaine’s protein binding in both adults and foals, thus lower lidocaine dosages are recommended when using any of these agents (Robertson  2012). While lidocaine CRIs may be beneficial in managing pain in foals, they should be used cautiously.

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12.7 ­Pain Management in the Donkey Donkeys have unusual characteristics that are different from horses. It is vital to appreciate these differences when understanding not only the assessment of pain but its treatment. Identifying pain behavior characteristics and responses to drug therapies in donkeys are ongoing. Pharmacologically, donkeys have been shown to demonstrate different distribution, metabolism, and elimination of various analgesic drugs compared with the horse (Grosenbaugh et al. 2011). Donkeys tend to be more stoic with their pain compared to horses, making then particularly difficult to assess. Oftentimes, severe pain gets overlooked (Matthews and van Loon  2019). Horse dosages are often used in donkeys due to a lack of education and data to support donkey-­specific dosing (Grint 2012).

12.7.1  Common Painful Conditions The three most predominant painful conditions in the older donkey are dental disorders, arthritis, and foot disorders. Gastric ulceration and gastrointestinal impaction follow that. Like many aged animals, elderly donkeys usually have dental disorders and arthritis. A donkey with dental disease is twice as likely to have a gastrointestinal impaction. Other common painful conditions include pancreatitis from hyperlipidemia and gastric ulceration (Morrow et al. 2011).

12.7.2  Pain Scoring and Behaviors Behavioral indicators have been used as a guide for identifying the presence of pain in a multitude of species. Diseases such as colic may go unobserved due to the absence of obvious pain indicators in donkeys. A horse will often kick and roll due to colic-­related pain (Crane 2002). However, a donkey will self-­ isolate. They may seem dull and unable to move –­frequently lying down.

12.7  ­Pain Management in the Donke

In some cases, they will carry their head low. In severe cases, paddling may occur (Whitehead et al. 1991; Crane 2002; Du Toit et al. 2010). Since behavioral changes tend to be more subtle in donkeys, it can appear as though a donkey is not in pain when in actuality it is (Lizarraga and Beths 2012). A pain assessment tool has been used on working donkeys where postural components of behavior and active behavioral events are scored. This tool includes measurable behaviors not altered by the time of day that would change after treatment (pharmacological

and palliative care) and behaviors that could be associated with severity of lesions. Pain assessment studies have revealed that meloxicam, when administered to donkeys experiencing painful conditions, altered not only grooming behavior but both head carriage and the rate of “eyes closing.” All four limbs also moved less when lameness was a factor (Regan et al. 2015). Pain assessments in donkeys is still evolving, but commonly accepted behavioral changes are noted in Table  12.4. Please see Chapter  4 for more on pain assessments.

Table 12.4  Behavioral indicators relating to the type of pain in the donkey. Type of pain

Behavioral indicator

Source

Head

Inability to chew properly, inappetence

Grint (2012)

Dental

Slow chewing one sided, quidding food portions cause discomfort, which can lead to weight loss

Trawford and Crane (1995)

Failure to attend feed and reluctant to move

Taylor and Matthews (1998)

Abdominal

Dullness, depression, self-­isolation, lethargy, lowered head carriage

Whitehead et al. (1991)

Colic

Head carried low, increased time lying down, and a reluctance to move

Du Toit et al. (2010)

Paddling of the feet (severe)

Whitehead et al. (1991)

Dullness

Crane (2002) and Grint (2012)

Respiratory disease

Subtle ear changes and lowered head carriage, increased time laying down

Olmos et al. (2011)

Failure to attend feed and reluctant to move

Taylor and Matthews (1998)

End-­stage hyperlipidemia

Subtle ear changes and lowered head carriage, increased time laying down

Olmos et al. (2011)

Paddling of the feet

Whitehead et al. (1991)

Failure to attend feed and reluctant to move

Taylor and Matthews (1998)

Keeping the foot lifted

Grint (2012)

Laminitis often unrecognized as posture is not altered in the donkey (such as it is in the horse)

Regan et al. (2015)

Increased time spent lying down

Trawford and Crane (1995)

Reluctance to move

Ashley et al. (2005)

Arthritis

Stiffness can accompany difficulty rising to standing

Whitehead et al. (1991)

Absence of pain

Walking, sniffing, and chewing or biting can indicate and ABSENCE of pain in working donkeys

Roy et al. (2010)

Lameness

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12  Pain Management in Equids

12.7.3  Anatomic and Physiologic Distinctions from the Horse There are unique anatomic and physiologic characteristics specific to pain management in the Jack and Jenny that veterinary technicians should be aware of. These differences may influence the approach to pain management in donkeys. Donkeys have adapted to desert climates and therefore can tolerate dehydration much more than the horse. Changes in hematocrit are often not seen until total body water loss is significant. Donkeys can maintain their plasma volume even when 20% dehydrated while horses cannot (Yousef et al. 1970). This adaptation will affect the clearance of analgesic drugs. Many of the analgesia drugs studied thus far have shown to have faster clearance times, and therefore donkeys have a comparatively greater ability than horses to both metabolize and eliminate drugs. Donkeys may have greater numbers and or movement of certain P450 isoenzymes than do horses; therefore, hepatically metabolized drugs might have a different dosing interval compared to that of a horse (Lizarraga et al. 2004). When it comes to intravenous catheterization of a donkey, the location is the same as the horse. However, donkeys have thicker skin, thicker cutaneous coli muscle, and an extra layer of facia than the horse.

12.7.4  Analgesics in Donkeys Common pharmacologic agents used for pain  management in donkeys are classified as  NSAIDs, alpha-­2 adrenoceptor agonists, opioids, and local anesthetics. Additionally, there are nontraditional drugs such as ketamine and tramadol, which will inhibit some painful responses. The use of these agents alone or in combination should be individualized for each donkey and should be based on the underlying cause of pain, duration, severity, degree of tissue trauma, sedation requirements, and health status. Preemptive analgesia

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Table 12.5  Opioid use in donkeys.

Opioids

Dosage (mg/kg)

Butorphanol

0.02–­0.05 IM, IV

Route

Duration

30–­60 min

Buprenorphine 0.006

IM, IV, 6 h Sublingual

Morphine

IM, IV

0.1

2–­3 h

should be administered whenever possible. Phenylbutazone, flunixin meglumine, butorphanol, and detomidine were shown to be the  most frequently used analgesics in 2009 by  UK veterinary respondents in a questionnaire (Grint  2012). Many veterinarians who answered this questionnaire prescribed drugs at the horse dosage rate which may be unsuitable in donkeys (Grint 2012). Dosing of analgesic therapies should be considered cautiously as various species of donkeys can have altered responses to drug therapies (Table  12.5). An example of this is the Mediterranean donkey, which seems to be more sensitive to sedative drugs and therefore may require a lower dosage (Matthews and Van Dijk 2004). 12.7.4.1  Agents

Nonsteroidal Anti-­inflammatory

Due to quicker elimination and a shorter ­half-­life in donkeys, NSAIDs such as flunixin ­meglumine and phenylbutazone should be administered at shorter intervals. Miniature donkeys metabolize flunixin meglumine faster than standard donkeys; therefore, there is a need to differentiate miniature from standard-­ sized donkeys. The suggested dosage rate is twice  daily in standard donkeys and three times daily in miniature donkeys (Matthews 2010). Carprofen appears to be metabolized slower in donkeys than in horses (Mealey et  al. 2004). Carprofen at 2 mg/kg by slow IV injection has been used in the donkey. A carprofen paste can be administered orally (2 mg/kg initially, followed by 1 mg/kg in 12 hours. and then 1 mg/kg every 12 hours).

12.7  ­Pain Management in the Donke

Meloxicam suspension (0.6 mg/kg once daily for  a maximum of 14 days) has also been used. A short half-­life with fast elimination and higher clearance suggests that current dosage practices of meloxicam in other species may not be clinically effective in donkeys (Sinclair et  al.  2006; Mahmood and Ashraf  2011). Acetaminophen (aka Paracetamol) is not commonly used in donkeys. This is most likely due to the short plasma level and half-­life (4 h

38

Butorphanol

Nalorphine

0.5 20–160

Lidocaine 1–2%

q12 h

60–165 min

Local infiltration or mixed in gel for superficial use 26

Dorsal lymph sac

Dexmedetomidine

a

Dorsal lymph sac

a

Xylazine

10

IC

q12–24 h

Codeine

53

Unspecified

>4 h

a

ED50 in leopard frog (R. pipiens)

ED50 in leopard frog (R. pipiens) Local anesthetic; use with caution

Ketorolac

40–120

ED50 in leopard frog (Rana pipiens)

>4 h

a

ED50 in leopard frog (R. pipiens)

a

ED50 in leopard frog (R. pipiens)

 Leopard frogs. Source: Adapted from Stevens (2004), West et al. (2007), Goldberg (2010), Stevens (2011), and Carpenter et al. (2013).

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14  Exotic Companion Animals

fish and amphibians and concluded there are no major distinctions between nociceptive afferent pathways in either mammals or amphibians and many fish; yet other comparative neurology suggests potential pain may be less substantial or recognized as such with these lesser vertebrates than in humans based on cerebral anatomy. With this said, fish and amphibians still do possess a well-­developed endogenous opioid system with corresponding binding sites, primarily kappa-­and delta opioid receptors. Not only do opioids provide analgesia but also there has been potential shown with other drugs like ketamine, alpha-­2 s, and tricaine methanesulfonate (Machin 1999; Stevens 2011). It is important to note that amphibians have a reduced rate of hepatic metabolism of certain medications and appear to require greater doses of opioids for systemic effect than mammals. In a study conducted using Eastern, red-­ spotted newts, the animals underwent a bilateral forelimb amputation. One group received systemic buprenorphine, while another had  a  bath application of butorphanol, and the  control group received no analgesics. The ­animals were then closely monitored for ­common signs of pain or discomfort ­associated with other species, such as poor appetite, spontaneous ­movement, and other species-­specific ­behaviors. The research did discover animals receiving the postoperative analgesics experienced shorter time to “normal” behaviors than the nontreatment animals. This suggested that pain potential is significant in amphibian species and can at least be partially controlled with opioid analgesics (Stevens 2011). Signs of pain in fish are subjective (body ­orientation and swimming, feeding, hiding, and/ or spatial positioning) (near aeration or heater), others are objective (environmental quality parameters, heart rate, opercular or respiratory rate, lethargy, fin clamping, darkening, blood diagnostic values, and/or physical examination findings) (Weber 2011). It is difficult to determine the nature of the response to pain in fish. Although they exhibit a pronounced response to injuries or to contact with irritants, their response to chronic stimuli may

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be small or absent. Fish with wounds that are severe enough to cause immobility in a mammal will often appear to behave normally and even resume feeding. Fish will react to noxious stimuli such as a hypodermic needle stick, by strong muscular movements. When exposed to a noxious environment, such as a strong acid, fish show abnormal swimming behavior with attempts to jump from the water. Their coloring becomes darker and opercular movements become more rapid. Such effects are indicative of some degree of distress; however, it is not possible to describe these unequivocally as signs of pain. The most predominant sign of distress or pain in fish is anorexia (Table 14.9). For more on fish and amphibian pain recognition please see Chapter 4.

14.8.1  Fish and Amphibian Treatment Strategies One of the advances in veterinary pain ­management is the use of transdermal patches that deliver analgesia through the skin. In amphibians, this has always been the case. Common anesthetic practices include anesthesia administration through the skin  and thus are the same with analgesics (West et al. 2007). A more controversial but still practiced form of anesthesia and analgesia is induced hypothermia. Possible animal welfare ­concerns can be made with this method, but one study has shown analgesic effect with ­hypothermia in northern leopard frogs (Stevens 2011). For fish, as well as amphibians, injectables can be given intramuscularly or added to the water in soaking tanks (Tables 14.10 and 14.11). However, many of the soaking methods are based on anecdote.

14.9  ­Analgesia in Invertebrates Very little is actually known about pain in invertebrates. For example, it is unclear if a wasp smashed with a flyswatter or a worm on a fishhook feels pain. All animal species can experience tissue damage. Invertebrates are a group of

14.9  ­Analgesia in Invertebrate

Table 14.9  Fish pain behaviors and clinical signs. Behavior

Description

Bottom sitting

Fish, typically found in middle or top of water column, “sitting” on bottom, not resting

Circling

Purposeful movement in one direction

Clamped fins

Fins held close to body wall

Coughing

Rapid opercular flaring

Curling

Body flexed laterally into a “C” shape

Abnormal coloration

Darker or lighter color than normal healthy, fish coloration

Drifting

Movement without purpose in the water currents

Feces: mucoid, bloody, long, with air bubbles, stringlike, pale

Analogous to diarrhea in terrestrial animals

Flared opercula

Opercula held open to expose gills

Flashing

Rubbing on bottom of tank or pond and exposing the ventral aspect (a “flash” of pale color of the ventrum)

Gasping

Yawning-­like behavior or rapid opening and closing of mouth

Hurdling

Apparent “falling” in water column followed by rapid forward/vertical movement

Jumping

Attempting to jump out of tank or pond (“suicide attempt”)

Listing

Leaning to one side

Pale coloration

Light version of normal is coloration

Petechiae/ecchymosis

Small red to purple spots on body surface, from pinpoint to larger focal areas (usually 4 mg not given 3 days

2–6.8 mg/ kg PO EOD – BIDm

ab

t

ac

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6 mg/kg PO SID – pudun

10–20 mg/kg PO then 2.5–5 mg/kg PO SIDi

4 mg/kg SC EOD for 2 dosesi

or 10 mg/kg PO q48i

1.0–3.0 mg/kg PO SID-­BIDx

s

 Nath et al. (2004).  Krauss et al. (2014). u  Molter et al. (2015). v  Ravasio et al. (2020). w  Goodnight et al. (2013). x  Citino and Bush (2007). y  Moresco and Larsen (2007). z  Arnemo and Evans (2017). aa  Fowler (2010).

2.8 mg/kg PO BIDi

*Banned in wildlife

 Aguilar and Superina (2015).  Hernandez et al. (2019). ad  Gjeltema et al. (2015). ae  Keller et al. (2012). af  Justo et al. (2021). ag  Witz et al. (2001). ah  Singh et al. (2019). ai  Murray et al. (2006).

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15  Analgesia in Zoo Animals

(a)

(b)

Figure 15.7  (a) A year-­old giraffe female was immobilized for enucleation after head trauma and was given flunixin meglumine orally both before and after the procedure, and IV during the procedure. The surgeon performed a retrobulbar block with 15 ml lidocaine 2% via the “supraorbital” fossa to block the optic nerve and cone for analgesia during the procedure. Following the surgical removal of the globe, the orbit was flushed with gentamicin (antibiosis in field anesthesia situation), and after complete closure, additional butorphanol and lidocaine were injected for local pain control. (b) Shows the same giraffe after recovery. Source: Courtesy Lion Country Safari.

Conditions such as foot abscesses or infections, toenail fractures, toenail overgrowth, and strain from being overweight take a huge toll on the health of elephants. Other painful and chronic degenerative ­conditions are seen in more aged  elephants, including osteoarthritis and neoplastic disease (Fowler  2007; Fowler and Mikota 2006). More acute conditions can occur, such as trauma from other herd members or predators, postsurgical incisions, and postpartum complications (Fowler and Mikota  2006). Recently, elephant endotheliotropic herpesvirus (EEHV) has emerged as the top contributor of mortality in infant and juvenile elephants of all subspecies in human care and native ranges. 15.7.1.1  Pain Interpretation

Pain interpretation can be challenging for ­multiple reasons in these giant creatures.

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There seems to be a common bias among inexperienced practitioners to underestimate pain due to the size and “toughness” of the elephant. In fact, elephants have very sensitive skin, despite being 2–3 cm thick in some places over the body. An elephant’s skin is sensitive enough to feel an insect land on it (Toit 2001). Facial coding has been attempted in elephants, but it is extremely subjective compared to established scoring methods in mice or rats. This is primarily due to the anatomy of an elephant’s face and its inability to show expression. Therefore, methods of interpreting pain, stress, and anger come from interpretations of the elephant’s eye position and openness, ear and tail positions, and trunk activities. An elephant may also kick to the front, side, or back as a sign of aggression either related to a threat or pain

15.7  ­Taxon-­specific Considerations

Table 15.2  Elephant pain queues. Anatomical feature

Normal position

Aggressive/painful positions

Eyes: elephants lack a lacrimal duct, therefore giving an appearance of crying as normal secretions drain down the side of the animal’s face

Open with eye engaged

Opened wide

Bright and well lubricated

Sclera visible

Clear discharge

Squinted

Trunk: the elephant’s trunk is a crucial part of its whole being; they eat, drink, smell, breath, lift, vocalize, and learn about their environment with it. It is comparable to the human hand with its use by an elephant

Engaged in its surrounding

Erect and trumpeting

Tossing dirt

Hanging with little movement

Ears

Flapping regularly

Erect

Alongside body in a relaxed elephant

Flapping vigorously

Brushing back and forth

Erect when preparing to charge or charging

Hanging when relaxed

Hanging when disengaged

Tail

Slapping the trunk with a burst of air to create a popping sound Uncoordinated movements or use

More vigorous slapping back and forth

(Fowler and Mikota  2006; West et  al.  2007) (Table 15.2; Figures 15.8–15.10). Inappetence is another key factor in ­determining elephant health status. Careful attention to diet and consumption is vital, especially in aged elephants who might be losing their last set of teeth. Thermal imaging is often used to evaluate regions of inflammation on elephant limbs (Fowler 2007) (see Figure 15.1). Most elephants in accredited facilities benefit from close relationships with their caregivers. The caregivers learn to recognize small nuances in an animal’s personality, which can be early indicators of clinical disease (Table  15.3). Early recognition of a potential problem is key to maximizing the success of potential treatments. A normal daily routine incorporated into an animals’ husbandry plan can be a good indicator of pain. For example, an animal may be asked to  participate in a training session every morning. If an animal is usually excited and interested in training but starts showing less interest or is slower to engage in certain

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behaviors like lifting a foot or laying down, this might indicate that something is wrong. Elephants of both species are hindgut fermenters and can experience colic, with ­symptoms similar to horses. These include symptoms of tenesmus, like frequent squatting and straining to expel the feces, along with restlessness, trunk biting, frequently sitting down and standing, inappetence, an abnormal posture with hind legs spread apart, and groaning (Khadpekar 2020). 15.7.1.2  Treatment

Most common medications found in a large animal veterinary clinic are sufficient for administration to elephants (Table 15.4). While many elephant-­appropriate dosages require large volumes of drugs, most common NSAIDs, opioids, and supplements are relatively simple to administer. Elephants, like any animal in abnormal health, may refuse medications at times. This can be an indicator of pain or discomfort. Drugs used to immobilize ­elephants such as thiafentanil or medetomidine also

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15  Analgesia in Zoo Animals

Figure 15.8  Elephant undergoing uncomfortable wound cleaning with ears flapping shows signs of irritation and discomfort. Source: Courtesy of Stephen Niño Cital.

Figure 15.10  An elephant with poorly managed feet leading to chronic pain.

Figure 15.9  This female Asian elephant is showing disengaged behavior after being struck by her mahout multiple times. Notice the lax trunk, partially closed eyes, and ears lying flat to the body. Source: Courtesy of Stephen Niño Cital.

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have analgesic properties (West et  al.  2007). Etorphine is a semi-­synthetic ­opioid possessing an analgesic potency approximately 1000–3000 times that of morphine (Bentley and Hardy  1967). Etorphine Large-­Animal Immobilon® (C-­Vet Veterinary Products,

15.7  ­Taxon-­specific Considerations

Leyland, UK) is a potent analgesic and is used in combination with other sedatives and ­induction agents. Many dosages for medications used in ­elephants, including local anesthetics for temporary pain relief, are extrapolated from horses or other large animal dosages. Other drugs, such as gabapentin at 6 mg/kg every 12 hours, have been prescribed for pain management in elephants, but formal pharmacokinetic studies have not been published. Adequan® (Polysulfated glycosaminoglycan – PSAG) was used in an African elephant with arthritis of the hip at a dose of 5 g once or twice weekly, with notable clinical improvement and exacerbation of signs during a 4-­week period Table 15.3  Common vocalizations or trunk activity in elephants.

Sound or activity

Possible interpretation

Blow or audible burst of air, sometimes with debris

Stress, irritation

Bellow

Pain or fear related

Scream

Excitement or anger

Trumpeting

Threat or excitement

Tapping with the tip of trunk

Self-­amusement or irritation

Musth rumble: deep and low, sometimes bubbly sounding

Indicating an animal in musth

when the drug was not given (Fowler and Mikota 2006). NSAIDs can be used to treat a number of acute and chronic pain issues in elephants. Flunixin meglumine and phenylbutazone are  two of the most common oral NSAIDs administered to elephants. A 2021 pharmacokinetic study of flunixin meglumine in Asian and African elephants shows that the two species react with different sensitivities to the drug and require different dosages. Asian elephants were reported to have faster peak serum concentration levels and longer duration, but at lower concentrations than African elephants, who reach a higher concentration for a shorter duration. It is recommended that Asian elephants should have a dosage regimen starting at 1 mg/kg, while African elephants have a ­dosage of 1.2 mg/kg (Bechert et al. 2021). Phenylbutazone has similar efficacy to flunixin meglumine but is thought to be more effective for treating skeletal pain, while flunixin is more effective for smooth muscle and visceral pain. Asian elephants have shown peak serum concentrations at a dosage of 2 mg/ kg every 48 hours and African elephants requiring 3 mg/kg every 24 hours along with clinical therapeutic effect (Bechert et al. 2008). Both drugs are reported to have similar adverse side effects and should be chosen based on the individual animals’ clinical presentation. While flunixin meglumine and phenylbutazone are the most often utilized NSAIDs in both

Table 15.4  Common analgesic for elephants. Drug

Dosage

Determining method

Ketoprofen

1–2 mg/kg

Pharmacokinetic

Butorphanol

0.05–0.1 mg/kg

Pharmacokinetic

Phenylbutazone

2 mg/kg Asian

Pharmacokinetic

3 mg/kg African q24h

Pharmacokinetic

1 mg/kg Asian

Pharmacokinetic

Flunixin

1.2 mg/kg African Ibuprofen

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6–7 mg/kg

Empirical

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15  Analgesia in Zoo Animals

species of elephants, according to the (Kottwitz et al. 2016) mega vertebrate ­analgesia survey of facilities housing either species conducted by the American Association of Zoo Veterinarians, many other NSAIDS are utilized including ibuprofen, which can be  administered at 6 mg/kg every 12 hours for Asian Elephants and 7 mg/kg every 12 hours for African elephants (Bechert and Christensen 2007). Firocoxib at a dosage of 0.1 mg/kg for both African and Asian Elephants is another alternative NSAID used to treat chronic arthritis and foot disease in both African and Asian elephants (Kottwitz 2019). Firocoxib at a dosage of 0.1 mg/kg for both African and Asian Elephants is another alternative NSAID used to treat chronic arthritis and foot disease  in  both African and Asian elephants (Kottwitz 2019). Meloxicam and ketoprofen are other NSAIDs commonly used in treating minor conditions such as soft-­tissue injuries, chronic osteoarthritis, and minor discomfort from normal herd interactions (Kottwitz et  al.  2016). Common side effects of NSAID administration in elephants are similar to other nonruminants and should be monitored. For more painful conditions such as skeletal fractures, deep open wounds, chronic dental disease, hemorrhagic disease caused by EEHV, and abscessed foot conditions caused by age or poor husbandry, opioids should be considered. While more studies are needed to assess appropriate drug and dosage regimens, anecdotal opioid use in a multi-­modal approach can provide additional analgesic options. Butorphanol is a widely used mixed agonist-­ antagonist opioid that elephants respond well to. It can be utilized in conjunction with sedation or anesthetic procedure or administered specifically for analgesia. The dosage range for butorphanol in elephants is surprisingly low given their size; 0.05–0.1 mg/kg is recommended (Kottwitz et  al.  2016). While it has limited efficacy as an analgesic, the sedative effects of butorphanol can help to relax animals who may be agitated by such discomfort as gastrointestinal (GI) colic. Tramadol is another synthetic opioid widely used to treat

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moderate to severe pain, although recent studies reveal a widely variable margin of efficacy; the most common dosage range among practitioners is 0.5–3 mg/kg, either as a sole agent or in combination with an NSAID (Kottwitz et al. 2016). While general anesthesia in elephants is rare, powerful opioids such as carfentanil, etorphine, and thiafentanil provide sufficient analgesia for tusk and molar extractions. The availability of these drugs may be dependent on geographical location as they become more widely regulated due to human abuse. Adjunct therapies for pain that are more recently being explored include stem cell ­therapy, therapeutic laser, acupuncture, and ­physical therapy. While the efficacy of these modalities is still widely anecdotal, they are innovative solutions for optimizing the quality of life of elephants in human care.

15.7.2  Great Apes Apes, particularly great ape species, are physiologically similar to humans. Much of their veterinary care, including medication recommendations and dosages, has been extrapolated from human medicine. This allows for a wide range of treatments for the management of pain. Consulting with human medical doctors should be considered a viable resource, though recommended treatment options may need to be modified for compliance and feasibility. Common analgesics include aspirin, acetaminophen, ibuprofen, meloxicam, gabapentin, and tramadol. Oftentimes a facility’s primate caretakers will be the first to notify veterinary staff of potential pain-­related concern. Even captive-­born apes will mask signs of discomfort, so keepers might have to pick up on even the smallest change in a normal routine. Some of these changes may include a decrease in appetite, refusing favorite food items or high-­value items, a decrease in activity, or a change in behavior. They may also present the part of their body that they are experiencing pain into a caretaker for examination.

15.7  ­Taxon-­specific Considerations

Apes are extremely intelligent. Toys, structures, and even diet items can be used in the management of pain and multimodal therapies. Talking with the animal care team about the animal, their personality, and what motivates them will help set up a successful treatment plan. This often involves finding a diet item that the animal is most likely to take medications in. Compounding medication is also something that can improve compliance, not only with taste but also with the volume of a prescribed dose. Some male gorillas weigh in excess of 200 kg, and as such may require large quantities of medication to achieve the effective dosage. Animals can be trained through operant conditioning to participate in their own medical care. Most apes have been conditioned to present various body parts to their caretakers. Utilizing these behaviors, the veterinary team can assess the ape. The ability to use diagnostic tools without anesthetic is beneficial to both the veterinary team and the animal. For example, obtaining awake radiographs to track arthritic changes in the hand of a geriatric orangutan can provide more information about how the ape is feeling versus what it is showing. This allows the veterinary team to adjust prescribed pain management protocols as necessary. Many multimodal techniques can also be safely administered through protective contact; an orangutan with osteoarthritis may be trained to present its hand to caregivers against the den mesh or through a training sleeve. This allows the care provider to safely administer rehabilitative therapy such as passive range of motion, cold laser therapy, or acupuncture. To further successful treatments, exhibits may be modified to include a sleeve, training platform, climbing structures, and items that require manipulation with hands and/or feet. These can be used in physical rehabilitation, increased accessibility, and strength training for animals with osteoarthritis, healing fractures, or muscle injuries. Allowing appropriate places to rest are also key. It can be difficult to force a gorilla to rest; setting up a minimalistic den with no climbing options and added bedding

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can encourage this behavior. Great apes, like humans, can be particularly sensitive to opioids; they may cause respiratory depression, hypotension, and constipation. Recent human trials and studies regarding the use of cannabidiol (CBD) as an analgesic offer another line of treatment options for chronic pain in apes and monkeys.

15.7.3  Old World and New World Non-­human Primates (NHP) The treatment of old and new world monkeys is very similar to techniques in small animals with the caveat of difficulty of administration for animals that are not trained. The use of analgesics in animals has received much attention in recent years, especially in laboratory animals where pain management is mandated by law and regulations (Hubbell and Muir 1996; Ramer et al. 1998). Administration of analgesia to nonhuman primates may be necessitated clinically by events such as trauma related to conspecific interactions in social housing, self-­injurious behavior, or injury from activity in the animal’s primary enclosure (Popilskis et  al.  2008). Analgesia may also be indicated in conjunction with study design that anticipates or produces a painful situation. Primates are wild animals, regardless of their origin (research or zoo animal), and as such they tend to mask signs of discomfort and pain. Observers may view changes in the animal’s behavior related to discomfort or pain. Repeated assessment, particularly after analgesic administration, can help focus on those signs that are most related to an individual primate’s pain (Murphy et al. 2012). Nonhuman primates show remarkably little reaction to surgical procedures or to injury, especially in the presence of humans, and might look well until they are gravely ill or in severe pain. Viewing an animal from a distance or by video camera can aid in detecting subtle clinical changes. A nonhuman primate

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that appears sick is likely to be critically ill and might require rapid attention. A nonhuman primate in pain has a general appearance of misery and dejection. It might huddle in a crouched posture with its arms across its chest and its head forward with a “sad” facial expression or a grimace and glassy eyes. It might moan or scream, avoid its companions, and stop grooming. A monkey in pain can also attract altered attention from its cage mates, varying from a lack of social grooming to attack (Figure  15.11). The animal may show acute abdominal pain through facial contortions, clenching of teeth, restlessness, and shaking accompanied by grunts and moans. Head pain may be manifest by head pressing against the enclosure surface. Self-­directed injurious behavior may be a sign of more intense pain. Primates in pain usually refuse food and water. If an animal is well socialized or trained to perform tasks as part of a research protocol, changes in response to familiar personnel or in willingness to cooperate may indicate pain. Common situations or procedures where analgesics are required in NHP medicine

Figure 15.11  A squirrel monkey experiencing pain after abdominal surgery.

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include management of perioperative and postsurgical pain (e.g. cesarean section or other laparotomy, orthopedic surgery, and digit amputation); minor surgical and diagnostic procedures such as laceration repair, biopsies, dental, and ophthalmic procedures; and management of pain associated with disease (including osteoarthritis) or trauma (Ramer et al. 1998). The use of a multimodal analgesic techniques for primates enables lower dosages of individual agents to be used, thereby reducing the possibility of side effects (Murphy et  al.  2012). The biggest consideration when administering analgesics to nonhuman primates is their sensitivity to opioids, which will  cause respiratory depression and severe hypotension under anesthesia (Figures  15.12 and  15.13). This speaks to the importance of  multimodal techniques in these species. A comprehensive formulary specific to nonhuman primates, which includes great apes and monkeys, can be purchased through www. primatevets.org.

Figure 15.12  A Vervet monkey that is not in pain showing a normal posture while engaged with its surroundings. Source: Courtesy of Stephen Niño Cital.

15.7  ­Taxon-­specific Considerations

small animals apply to NHPs. Nocita® has been used successfully in several NHP species. Monkeys in captivity also tend to suffer from varying forms of dental disease, either cavities or fractures of teeth, to severe attrition leading to pulp exposure. The same methods used in small animals apply to dentistry in NHPs. In Figures  15.14–15.17 we see familiar dental blocking techniques that can be used in NHPs for surgical extractions. See Chapter  6 for descriptions.

Figure 15.13  A blue-­eyed lemur that is hunched and unkempt in appearance. This animal may have slight discomfort. Source: Courtesy of Stephen Niño Cital.

15.7.3.1  Signs of Pain or Distress in Nonhuman Primates ●● ●● ●● ●● ●● ●● ●● ●● ●● ●● ●●

Aggression Apprehensive facial expression Ataxia Clenching of teeth Crouched position with arms across chest Decreased activity Decreased vocalization Loss of appetite Rocking Self-­biting or self-­mutilation Vocalization (grunts and moaning)

Figure 15.14  A maxillary molar block.

Recently, Paterson et al. (2023) published the first grimace scale for cynomolgus macaques that can likely be used for other macaque species. 15.7.3.2  Local and Regional Anesthetics

Local and regional anesthetic techniques have been used in nonhuman primates to block transduction and transmission of painful stimuli. The same principles and dosages used in

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Figure 15.15  Mental nerve block technique.

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Figure 15.16  Inferior (caudal) alveolar nerve block (extraoral).

Figure 15.17  Infraorbital nerve block.

15.7.4  Exotic Ungulates In all ungulates, the importance of preventive hoof care should be stressed as the most effective method to control discomfort. Hoof misalignment, overgrowth, and abscesses can lead to chronic pain and arthritis in proximal joints. The lack of pharmacokinetic studies in exotic

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ungulate species leads to a highly variable analgesic approach to pain management. Drug choice, dosage, and frequency are extrapolated from the closest related species, often those in the livestock production industry. A survey study into the current use of analgesics in megavertebrates has shown there is no real standard when choosing a medication or a dosage (Boothe et  al.  2016; Kottwitz et  al.  2016). Additional research into the pharmacokinetics of analgesics is needed. When evaluating pain management in ungulates, it is tempting to want a one-­size-­fits-­all approach, but this is not practicable. Potential medication administration routes are oral, IM, subcutaneous (SC), intravenous (IV), and epidural. Many of these are used in domestic livestock medicine. Zoo and wildlife ungulates present the additional challenges of being high-­stress nontactile animals, and medications affect species differently. The varying GI tract functions of ungulates have a lot of influence on medication efficacy and protective precautions must be taken with long-­term use of NSAIDs. Potential adverse reactions to analgesics include GI stasis, diarrhea, and GI ulcerations. GI stasis is more commonly seen with the use of opioids such as butorphanol, tramadol, and fentanyl. GI ulcerations, bloody stool, and diarrhea are more commonly seen with the use of NSAIDs, including meloxicam, flunixin meglumine, and phenylbutazone. Some GI reactions may not be perceived clinically but would be seen on necropsy. As a further complication, all gastroprotectants are considered off-­label and effective options are limited. There are a few studies looking into the utilization of specific medications in particular species (Ahmed et al. 2005). In cattle, famotidine administered intravenously in conjunction with analgesics has been shown to have protectant effects, but it must be given multiple times a day, which precludes treatment of animals that cannot be regularly approached (Balcomb et  al.  2018). According to the Zoological Information Management System (ZIMS), oral omeprazole, famotidine, and

15.7  ­Taxon-­specific Considerations

ranitidine have been used in giraffes. Omeprazole was the most common gastroprotectant administered to zebras. Ranitidine and famotidine were also used without adverse effects (ZIMS Drug Usage Extracts 2022). The success of pain management is very much dependent on the individual animal. Utilizing exhibit design and chutes for direct access may make treatments easier. Many institutions integrate operant conditioning with their normal daily husbandry, including work in a drop-­floor chute. When a chute is not available, voluntary operant conditioning is crucial. Training can include hoof care, injections, blood draw, tactile desensitization, radiographs, and other specific hands-­on treatment needs. When neither chute nor training are options, treatment feasibility needs to be considered in the pain management plan. Will the animal take oral medications? Does it need to be compounded? Will the animal need to be darted? How frequently? Are sustained-­release formulations available? Will anesthesia be necessary to treat? What are the risks? 15.7.4.1  Nonruminant Ungulates

Nonruminants comprise the order perissodactyla, or odd-­toed ungulates, and include equids, rhinoceros, hippopotamus, and tapir. Osteoarthritis, hoof disease, dental disease, and colic are common disease processes that cause significant pain in this taxon. Animal compliance is essential when working with these megavertebrates, as a 1000 kg animal cannot be safely restrained to perform foot care, wound care, or any therapies without its willing participation. The current most common analgesics are phenylbutazone and flunixin meglumine. Fircoxib, meloxicam, butorphanol, and tramadol use have also been reported to a lesser extent. Prolonged administration or high-­dosage administration of NSAIDs may lead to GI ­ulceration, renal damage, colitis, or toxicosis. Phenylbutazone has been shown to have a higher ulcerogenicity than other commonly used NSAIDs (Stewart 2022). Clinical signs of GI ulceration

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are similar across ungulates and may include anorexia, colic, and diarrhea. Toxicosis may cause oral and esophageal ulcerations. This may manifest as hypersalivation, difficulty swallowing, and pain when chewing. There are limited studies on the effects of current analgesics in exotic hoofstock, particularly megavertebrates. A pharmacokinetic study evaluated the efficacy of a single oral dosage of flunixin meglumine (1 mg/kg) in a white rhinoceros. The results showed that the animal was able to absorb and metabolize the flunixin meglumine, but also suggested that this was at a slower rate than other species. While more studies are needed, it showed that this dosage was safe for white rhinoceros (East et  al.  2019). A survey of zoological facilities compiled a listing of drugs, dosages, administration routes, and perceived efficacy for ­elephant, rhino, hippo, and giraffe (Boothe et  al.  2016; Kottwitz et  al.  2016). Treatments developed for domestic equine species are also extrapolated for use in exotic equids. In a real-­life scenario, a zoo in North America cares for a geriatric herd of female Grevy’s zebra (Equus grevyi). The average age at the time of publication is 20 years. Common ailments of the geriatric herd include osteoarthritis, poor hoof wear and/or abscesses, and colic. Flunixin meglumine (1 mg/kg) and meloxicam (0.5 mg/kg) are common analgesics for the treatment of colic. Phenylbutazone (2.2–4.4 mg/ kg every 12–24 hours) is commonly used for musculoskeletal pain; however, it is associated with oral and GI ulceration with long-­term use at high dosages and is contraindicated in equines with renal or GI disease. Flunixin meglumine is considered safer and similar in efficacy (Malone et  al.  2022). All have been used for pain management, in  combination with omeprazole as a gastroprotectant, in the herd. For example, an individual with chronic intermittent colic-­like episodes received flunixin meglumine injectable (1 mg/kg) IM as an initial treatment followed by a course of meloxicam (0.5 mg/kg) orally once daily. Omeprazole paste (4 mg/kg) was added in combination with the

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NSAIDs. The course of omeprazole is longer than the course of NSAIDs for GI protection. Another individual has had infrequent occurrences of lameness. These incidents have been associated with resolving abscesses, hoof wear, and acute trauma. The advanced age of this individual was a consideration for choosing flunixin meglumine over phenylbutazone for analgesia. Various treatments have included a short course of flunixin meglumine (1 mg/kg) paste once daily, a single dose of flunixin meglumine IM given during a hoof management exam, and meloxicam (0.5 mg/kg) orally once daily, all in combination with omeprazole. The zoo has been able to manage chronic and acute pain in the herd with these medications. Nonpharmaceutical treatments include cold laser therapy, acupuncture, chiropractic, and pulsed electromagnetic field therapy (PEMF). These treatments require the willing participation of the individuals. The utilization of chutes has aided in the success of the multimodal treatments. 15.7.4.2  Ruminant Ungulates

The use of NSAIDs is common in ruminant medicine; most commonly used are phenylbutazone, flunixin meglumine, ketoprofen, ­firocoxib, and meloxicam (Boothe et  al.  2016; Kottwitz et al. 2016). The most common adverse reactions involve the GI system and range from inappetence to diarrhea. Monitoring for blood in the stools can be done by running a fecal occult blood test. If the NSAID is at the higher end of the dosage or if it will be administered for a long period of time, a GI protectant can be given to minimize the effects of the NSAID on the GI system. In 2014 at a zoo in North America, a multimodal approach was used in the pain management of a 15-­year-­old female reticulated giraffe (Giraffa camelopardalis reticulata) with chronic fetlock osteoarthritis with supination in the left fetlock. The pain management was adjusted as the giraffe aged and the status of pain or discomfort changed. Initial treatments included a 2-­day course of flunixin meglumine

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750 mg (1 mg/kg) for acute pain. This was transitioned to a course of phenylbutazone orally twice daily. The initial dosage was 3 mg/kg for 5 days and then increased to 4 mg/kg for 30 days. When an increase in pain and discomfort was appreciated, integrative pain management was added to the multimodal therapy and analgesics were modified. These integrative therapies included low-­level laser, PEMF, acupuncture, ice wrap, and a specially designed corrective orthotic boot to help brace the hoof and stabilize the fetlock joint. Oral analgesics were then adjusted to long-­term meloxicam (0.1–1.0 mg/kg) and gabapentin (2–19 mg/kg). Topical analgesics included diclofenac (13 mg) and lidocaine (50 mg) patches as needed. In 2019, tramadol (0.5 mg/kg) orally twice daily was added to the analgesic therapy regime. Thermography was used to visualize the efficacy of the ice wraps as well as pain flare-­ups. This pain management regimen continued for 6 years. By utilizing a lameness chart, keepers and veterinary staff were able to track the progression of the giraffe’s arthritis and adjust treatments as necessary. The cause of an ungulate’s pain may not be chronic like osteoarthritis; it might be acute from injury or surgery. A male okapi (Okapia johnstoni) in North America was induced for a general anesthetic procedure for a diagnostic physical exam due to weight loss, exaggerated licking and chewing, and a recheck of a resolved maxillary mass. Induction was accomplished with medetomidine 8 mg (0.037 mg/kg), thiafentanil 1.3 mg (0.006 mg/ kg), ketamine 200 mg (0.93 mg/kg), and butorphanol 9.6 mg (0.045 mg/kg). Each of these drugs has analgesic properties, which means the animal had pain management on board during the procedure for any potentially painful diagnostics. Due to the need for rapid recovery in zoo ungulates, the opioids were reversed at the end of the procedure, which terminated the analgesic effect from those drugs. Just before recovery, flunixin meglumine 215 mg (1 mg/kg) injection was administered intramuscularly for one dose. This was

15.7  ­Taxon-­specific Considerations

followed by oral meloxicam 105 mg (0.05 mg/ kg) once per day until a second procedure was performed to collect biopsy samples. The same general anesthesia protocol was used. Prior to the end of the procedure, the okapi received meloxicam 40 mg (0.2 mg/kg) IM. Upon anesthetic recovery, oral meloxicam 90 mg (0.42 mg/kg) was administered once a day for 14 days and tramadol 400 mg (1.86 mg/kg) was administered once a day for 10 days. The keepers were able to monitor the okapi’s pain based on its willingness to eat its normal favorite diet items. No additional pain management was required. At a zoo in the United States, CBD was used in the multimodal treatment of a Bactrian camel (Camelus bactrianus) with osteoarthritis. CBD has been shown in studies to decrease inflammation and provide pain relief in companion animals. Studies are ongoing in its use  for livestock species. The availability of CBD varies by state and country. Currently, veterinarians are not allowed to prescribe CBD. Private owners and zoos can seek out supplements on their own if it is legal in their respective states.

15.7.5  Swine Suids in general are prone to hoof disorders, injury by conspecifics, and tooth/tusk fractures; each of these presents its own challenges in treatment. See Chapter 13 for more detail on analgesia in domestic swine/pigs. The hooves of suids are softer compared to those of other ungulates. This predisposes them to abrasions and embedding foreign bodies, such as rocks, that may cause abscesses (Figure  15.18). Cracks in the hoof wall, often caused by overgrown claws, have also led to lameness. Proper hoof care is important for exotic suids (Miller and Fowler 2015). This can be accomplished by free or protective contact operant conditioning. The choice to manage with free vs. protective contact is at the ­discretion of the institution. If the animals are not trained for hoof care, routine general

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Figure 15.18  A boar with a laceration to its foot.

anesthetic exams may be required. Chronic cases may require frequent anesthetic procedures. These procedures may be preventative or based on a lameness incident. Exotic suids are often aggressive with one another, especially as males age and attempt to establish dominance. Wound injuries caused by this aggression are very common and are seen in both captive and wild populations. Reintroductions following a period of separation for a group member, such as an anesthetic procedure, can lead to a wound injury as individuals reestablish hierarchy. Effective wound management of an individual should include herd management considerations. Medications that may cause a sedative effect should also be considered carefully, as this may affect how the suid is able to defend or escape an injury. Exotic suid species can possess large tusks in both males and females, though males’ are larger. The size and shape of the tusks inform the risk of fractures (Miller and Fowler 2015). Pain associated with tusk fractures may affect oral medication compliance. Training exotic suids for voluntary hand injection can limit the need for darting of medications and reduce the risk of further tusk injury.

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The use of transdermal fentanyl patches has been used in domestic swine for sustained release pain management. Placement can be behind the ear or dorsal interscapular region. Current studies suggest 50 mcg/h provided pain management in domestic swine 20–30 kg (Miller et al. 2019). However additional studies of the efficacy of this treatment in zoo and wildlife species are needed. At a zoo in North America, a male intact red river hog (Potamochoerus porcus) had a chronic history of poor hoof condition. In 2008, at 1 year of age it was reported to have severe hind limb lameness, likely caused by a conspecific. A short course of oral flunixin meglumine 50 mg (2 mg/kg) orally once daily was started, and improvement was observed. Frequent fighting in red river hogs is not an abnormal behavior as they establish hierarchy within a litter. This same course was prescribed following any subsequent incident that resulted in lameness. In 2009, the hog was transferred to another North American zoo to be paired with a female for recommended breeding. It was reported that the animal had sustained abrasions on all four feet, causing lameness, 7 days after arriving at the zoo. Tramadol 50 mg (1 mg/ kg) orally twice daily was prescribed. At the animal’s quarantine exam, lesions on the medial claws along with bruising and swelling at the coronary bands were noted. A single injection of flunixin meglumine 62.5 mg (1.2 mg/kg) was given intramuscularly. The following day the hog was started on a course of carprofen (100 mg) orally twice daily. A gastroprotectant, omeprazole 45 mg (0.9 mg/kg) orally once daily was also prescribed. A follow­up procedure showed the lesions to be clean, but larger. Protective caps were applied to all claws. Tramadol was prescribed for 45 days. At a follow-­up procedure, the lesions on the front claws appeared improved. The rear claws had signs of infection and deepening of the lesions. The claws were bandaged, and carprofen and omeprazole were prescribed until further notice. This was the beginning of every other day general anesthetic procedures to treat and

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dress the infection that had started in the rear medial claws. Trial and error eventually led to a bandage style that provided protection and cushioning but didn’t easily come off. As the feet began to heal, bandage changes were decreased in frequency to twice a week to weekly over a four-­month period. During that time the hog received diazepam 30 mg (0.6 mg/ kg) twice daily to sustain slight sedation. This period of hoof injury and infection led to chronic hoof care needs. The hog was susceptible to rocks burrowing into the sole of the claws, hoof abscesses, and overgrown claws. It also predisposed the animal to early onset osteoarthritis. It was started on glucosamine 3 g (40 mg/kg) orally twice daily for joint ­support shortly after the hooves healed. Meloxicam 15 mg (0.2 mg/kg) orally once daily and/or tramadol 150 mg (2 mg/kg) orally twice daily were prescribed when lameness was noted by keepers. These treatments continued for 12 years. Gabapentin 600 mg orally twice daily was prescribed at the last presentation of lameness. This was discontinued the following day when humane euthanasia was elected due to the progression of osteoarthritis. Appropriate analgesic support allowed the red river hog to have a good quality of life, remain active interacting with keepers and its mate, sire four litters, and assist in raising the young.

15.7.6  Wildlife The possibility of wildlife or game animals entering the food chain is a consideration for any drug use in the field. In the United States, there are currently no analgesics labeled for use in wildlife. The use of any medication would be considered extra label drug use (ELDU). A few drug classes have been ­completely banned in the USA for use in any animal that may enter the food chain, meaning that an animal intended for consumption may never receive these drugs. These include fluoroquinolones and cephalosporins. Phenylbutazone is the only prohibited analgesic (AVMA  2003). Much of the information

 ­Reference

on wildlife dosages is extrapolated from major commercial domestic species such as cattle, swine, and equine, and minor species such as  goats and sheep. Withdrawal interval (WDI) recommendations can be found in the Food Animal Residue Avoidance Databank (FARAD). In the United States, any game animal that has received medications needs to be identified with a permanent tag. Historically that just included animals that were within 30 days of their hunting season. Many states now have regulations regarding roadkill and the salvaging of carcasses and as such, it is best practice to tag any game animal that has received any medications. This tag has the  state’s Department of Fish and Wildlife’s phone number and an ID number. The ID number will connect the animal to its ­individual records of medications used (WDFW 2022). There is currently no universal tag. Each state’s Department of Fish and

Wildlife veterinarian should be able to provide tag information. http://www.farad.org/publications/digests/ 090119ExtralabelinWildlife.pdf; AVMA https:// www.avma.org/javma-­n ews/2003-­0 4-15/ extralabel-­use-­phenylbutazone-­banned-­dairycattle; WDFW https://wdfw.wa.gov/hunting/ requirements/food-­safety/tagged-­game

15.8  ­Conclusion Empathy is a driving force behind advocating for the well-­being of other living creatures. It is empathy for all living creatures that drives innovation in the field of pain management. Just as veterinary medicine has excelled over the past decade in its understanding of common zoological species, it is also propelling improvements in analgesia for widely varying taxa.

­References Aguilar, R.F. and Superina, M. (2015). Xenarthra. In: Zoo and Wild Animal Medicine, vol. 8 (ed. M. Fowler and R.E. Miller). Missouri: Saunders. Ahmed, A.F., Constable, P.D., and Misk, N.A. (2005). Effect of orally administered omeprazole on abomasal luminal pH in dairy calves fed milk replacer. Journal of Veterinary Medicine A 52: 238–243. Amass, K. and Drew, M. (2012). Chemical Immobilization of Animals: Technical Field Notes 2011. Mt. Horeb, WI: Safe-­Capture International, INC. Section 2-­1. Arnemo, J.M. and Evans, A.L. (2017). Biomedical Protocols for free-­ranging brown bears, wolves, wolverines and lynx. https://brage.inn.no/ inn-­xmlui/bitstream/handle/11250/2444409/ Biomedical%20Protocols%20Carnivores%20 2017.pdf?sequence=1 (accessed 29 May 2024). AVMA (2003). Extralabel use of phenylbutazone banned in dairy cattle. https://www.avma.org/ javma-­news/2003-­04-­15/extralabel-­use-­

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phenylbutazone-­banned-­dairy-­cattle (accessed 29 May 2024). Balcomb, C.C., Heller, M.C., Chigerwe, M. et al. (2018). Pharmacokinetics and efficacy of intra-­venous famotidine in adult cattle. Journal of Veterinary Internal Medicine 32: 1283–1289. Bechert, U. and Christensen, J.M. (2007). Pharmacokinetics of orally administered ibuprofen in African and Asian elephants (Loxodonta africana and Elephas maximus). Journal of Zoo and Wildlife Medicine 38 (2): 258–268. Bechert, U, Christensen, JM, Nguyen, et al. (2008). Pharmacokinetics of orally administered phenylbutazone in African and Asian elephants (Loxodonta africana and Elephas maximus). Journal of Zoo and Wildlife Medicine 39 (2): 188–200 doi: 10.1638/2007-0139R.1. PMID: 18634209. Bechert, U., Christensen, J.M., Kottwitz, J. et al. (2021). Pharmacokinetics of orally administered Flunixin Meglumine in African

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(Loxodonta africana) and Asian (Elephas maximus) elephants. Journal of Zoo and Wildlife Medicine 51 (4): 905–914. Bentley, K.W. and Hardy, D.G. (1967). Novel analgesics and molecular rearrangements in the morphine-­thebaine group. 3. Alcohols of the 6,14-­endo-­ethenotetrahydrooripavine series and derived analogs of N-­allylnormorphine and -­norcodeine. Journal of the American Chemical Society 89 (13): 3281–3292. Boothe, M., Kottwitz, J., Harmon, R. et al. (2016). Results of the megavertebrate analgesia survey: giraffe and hippopotamus. Journal of Zoo and Wildlife Medicine 47 (4): 1049–1056. Bradley, T. (2001). Pain management considerations and pain-­associated behaviors in reptiles and amphibians. In: AAZV, AAWV, ARAV, NAZWT Joint Conference Proceedings. Carpenter, J. and Harms, C. (ed.) (2022). Carpenter’s Exotic Animal Formulary, 6e. St. Louis, Missouri: Elsevier. Citino, S. and Bush, M. (2007). Giraffidae. In: Zoo Animal and Wildlife Immobilization and Anesthesia (ed. G. West, D. Heard, and N. Caulkett), 605. Iowa: Blackwell. Citino, S. and Zuba, J. (2012). Analgesia for the “big-­uns,” elephants, rhinos, giraffes and hippos. In: 2012 AAZV Proceedings. Collins, D.M. (2015). Ursidae. In: Zoo and Wild Animal Medicine, vol. 8 (ed. M. Fowler and R. Miller), 501. Missouri: Saunders. Conzemius, M. (2012a). Analgesia in zoo and wildlife animals: translating and creating evidence. In: 2012 AAZV Proceedings. Conzemius, M. (2012b). The science of measuring perioperative pain. In: 2012 AAZV Proceedings. East, B., Tell, L., Citino, S.B.M. et al. (2019). Pharmacokinetics of a single oral dose of flunixin meglumine in the white rhinoceros (Ceratotherium simum). Journal of Zoo and Wildlife Medicine 50 (2): 322–329. Fowler, M. (2007). Zoo and Wild Animal Medicine Current Therapy, 6e. Saunders. Fowler, M.E. (2010). Medicine and Surgery of Camelids, 3e. Iowa: Blackwell.

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Fowler, M. and Mikota, S. (2006). Biology, Medicine, and Surgery of Elephants. Ames IA: Blackwell Publishing. Galloway, D.S. et al. (2002). Spinal compression due to Atlantal vertebral malformation in two African lions (Panthera leo). Journal of Zoo and Wildlife Medicine 33 (3): 249–255. Gjeltema, J.L., MacLean, R.A., Cohen, E.B., and DeVoe, R.S. (2015). Hypertrophic osteodystrophy in two red wolf (Canis rufus) pups. Case Reports in Veterinary Medicine 2015 (11): 1–6. Goodnight, A.L. et al. (2013). Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta). Journal of Zoo and Wildlife Medicine 44 (4): 1068–1074. Gozalo Marcilla, M., Bosmans, T., Hellebuyck, T. et al. (2010). Anesthetic and analgesic management of a skunk (Mephitis mephitis) undergoing a laminectomy for cauda equina compression. Vlaams Diergeneeskundig Tijdschrift 79 (5): 395–399. Gunkel, C. and Lafortune, M. (2007). Felids. In: Zoo Animal and Wildlife Immobilization and Anesthesia (ed. G. West, D. Heard, and N. Caulkett), 89. Iowa: Blackwell. Hahn, A. (2019). Zoo and Wild Mammal Formulary, 630. Newark: Wiley. Print. Hahn, N., Parker, J., Timmel, G. et al. (2014). Hyenas. In: Zoo Animal and Wildlife Immobilization and Anesthesia, 2e (ed. G. West, D. Heard, and N. Caulkett). Iowa: Blackwell. Heard, D. (2014). Chiropterans (bats). In: Zoo Animal and Wildlife Immobilization and Anesthesia, 2e (ed. G. West, D. Heard, and N. Caulkett), 543. Iowa: Blackwell. Hernandez, S., Barron, H. Miller, E. et al. (2019). Medical Management of Wildlife Species -­A Guide for Practitioners Hoboken, New Jersey. Herrin, K.V., Allan, G., Black, A. et al. (2012). Stifle osteochondritis dissecans in snow leopards (Uncia uncia). Journal of Zoo and Wildlife Medicine 43 (2): 347–354. Hawkins, M.G., Barron, H.W., Speer, B.L. et al. (2013). Birds. In: Exotic Animal Formulary, 4th ed. (ed. J.W. Carpenter), 203–457. St. Louis: Elsevier-Saunders.

 ­Reference

Howard, L.L. and Richardson, G.L. (2005). Transposition of the biceps tendon to reduce lateral scapulohumeral luxation in three species of nondomestic ruminant. Journal of Zoo and Wildlife Medicine 36 (2): 290–294. Hubbell, A.E. and Muir, W. (1996). Evaluation of a survey of the diplomates of the American College of Laboratory Animal Medicine on use of analgesic agents in animals used in biomedical research. Journal of the American Veterinary Medical Association 209 (5): 918–921. Justo, A.A., Garofalo, N.A., Teixeira-­Neto, F.J. et al. (2021). Epidural anesthesia in Eira barbara Linnaeus, 1758 (Carnivora: Mustelidae). Brazilian Journal of Biology 81 (2): 495. Keller, D.L., Ellison, M., Clyde, V.L., and Wallace, R.S. (2012). Accessory carpal bone luxation in two gray wolves (Canis Lupis). Journal of Zoo and Wildlife Medicine 43 (3): 657–661. Khadpekar, Y. (2020). Clinical management of intestinal impaction and colic in an Asian elephant. Gajah 51: 26–30. https:// www.asesg.org/PDFfiles/2020/ 51-­26-Khadpekar.pdf. Kottwitz, J.R. (2019). Determination of Safe and Effective Dosing Regimens for Nonsteroidal Anti-­inflammatory Drugs in African and Asian Elephants. [PhD, Auburn]. http://hdl. handle.net/10415/6902 Kottwitz, J. et al. (2016). Results of the megavertebrate analgesia survey: elephants and rhino. Journal of Zoo and Wildlife Medicine 47 (1): 301–310. Krauss, M.W. et al. (2014). Intervertebral disk disease in 3 striped skunks (Mephitis mephitis). Veterinary Surgery 43 (5): 589–592. Larsen, R. and Kreeger, T. (2007). Canids. In: Zoo Animal and Wildlife Immobilization and Anesthesia (ed. G. West, D. Heard, and N. Caulkett), 594–595. Iowa: Blackwell. Larsen, R., Cebra, C., and Wild, M. (1997). Surgical Correction of Urethral Obstruction in an Elk by Perineal Urethrostomy. AAZV Proceedings 1997.

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Lee, S.Y. et al. (2014). Unilateral laparoscopic ovariectomy in a red fox (Vulpes vulpes) with an ovarian cyst. Journal of Zoo and Wildlife Medicine 43 (3): 678–681. Machin, K. (2007). Wildlife analgesia. In: Zoo Animal and Wildlife Immobilization and Anesthesia (ed. G. West, D. Heard, and N. Caulkett), 1–5. Iowa: Blackwell. Malmlov, A., Campbell, T., Monnet, E. et al. (2014). Diagnosis, surgical treatment, recovery, and eventual necropsy of leopard (Panthera pardus) with thyroid carcinoma. Case Reports in Veterinary Medicine 2014 (2): 1–5. Malone, E., Norton, E., Dobbs, E., and Ezzo, A. (2022). Large Animal Surgery -­Supplemental Notes, Equine Drugs, Equine NSAIDS and Analgesics. https://open.lib.umn.edu/ largeanimalsurgery (accessed 29 May 2024). Miller, R.E. and Fowler, M. (2015). Zoo and Wild Animal Medicine Current Therapy, vol. 8. Saunders. Miller, R.E., Lamberski, N., and Calle, P.P. (2019). Fowler’s Zoo and Wild Animal Medicine Current Therapy, vol. 9. Saunders. Molter, C.M., Jackson, J., Clippinger, T.L., and Sutherland-­Smith, M. (2015). Tibial plateau leveling osteotomy in a cape clawless otter (Aonyx capensis) with cranial cruciate ligament ruptures. Journal of Zoo and Wildlife Medicine 46 (1): 179–183. Moresco, A. and Larsen, S. (2007). Viverrids. In: Zoo Animal and Wildlife Immobilization and Anesthesia (ed. G. West, D. Heard, and N. Caulkett), 620. Ames, IA: Wiley-­Blackwell. Murphy, K.L., Baxter, M.G., and Flecknell, P.A. (2012). Anesthesia and analgesia in nonhuman primates. In: Nonhuman Primates in Biomedical Research Volume 1: Biology and Management, American College of Laboratory Animal Medicine Series, 2e (ed. C.R. Abee, K. Mansfield, S. Tardif, and T. Morris), 432–433. London, UK: Elsevier/ Academic Press. Murray, M. (1996). Nonsteroidal anti-­ inflammatory drug toxicity. In: Large Animal Internal Medicine, 2e (ed. B. Smith), 306–307. Missouri: Mosby.

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Murray, S., Sanchez, C.D., Siemering, G.H. et al. (2006). Transitional cell carcinoma of the urinary bladder in a spectacled bear (Tremarctos ornatus). The Veterinary Record 158 (9): 306–307. Nath, I., Bose, V.S.C., Panda, S.K. et al. (2004). Conservative management of metatarsal fracture in a tiger (Panthera tigris). Zoos’ Print Journal 19: 1670–1670. Paterson, E.A., O’Malley, C.I., Moody, C. et al. (2023). Development and validation of a cynomolgus macaque grimace scale for acute pain assessment. Scientific Reports 13 (1): https://doi.org/10.1038/s41598-­023-30380-­x. Popilskis, S.J., Lee, D.R., and Elmore, D.B. (2008). Chapter 12 Anesthesia and analgesia in nonhuman primates. In: Anesthesia and Analgesia in Laboratory Animals, American College of Laboratory Animal Medicine Series, 2e (ed. R.E. Fish, M.J. Brown, P.J. Danneman, and A.Z. Karas), 336–363. London, UK: Elsevier/Academic Press. Ramer, J.C., Emerson, C., and Paul-­Murphy, J. (1998). Analgesia in Nonhuman Primates. In: Proceedings AAZV and AAWV Joint Conference, 480–483. Ramsay, E. (2008). Use of analgesics in exotic felids. In: Zoo and Wild Animal Medicine Current Therapy, vol. 6 (ed. M. Fowler and R. Miller), 479. Missouri: Saunders. Ramsay, E.C. (2014). Felids. In: Zoo Animal and Wildlife Immobilization and Anesthesia, 2e (ed. G. West, D. Heard, and N. Caulkett), 89–91. Ames, IA: Wiley-­Blackwell. Ravasio, G., Brioschi, F.A., Rabbogliatti, V. et al. (2020). Case report: ultrasound sciatic and saphenous nerve blocks for tibial Malunion surgical correction in a pediatric African leopard (Panthera pardus). Frontiers in Veterinary Science 7: 538883. Singh, J., Verma, R.K., Sharda, R. et al. (2019). Fore limb amputation following complicated fracture in a striped hyena (Hyaena hyaena). Journal of Entomology and Zoology Studies 7 (2): 650–653.

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Souza, M. and Cox, S. (2011). Tramadol use in zoologic medicine. The Veterinary Clinics of North America. Exotic Animal Practice 2011 14: 117–130. Spriggs, M., Arble, J., and Myers, G. (2007). Intervertebral disc extrusion and spinal decompression in a binturong (Arctictis binturong). Journal of Zoo and Wildlife Medicine 38 (1): 135–138. Stewart, A. (2022). NSAID Toxicosis and Right Dorsal Colitis (RDC) in Horses. https://www. merckvetmanual.com/digestive-­system/ miscellaneous-­intestinal-­diseases-­in-­horses/ nsaid-­toxicosis-­and-­right-­dorsal-­colitis-­rdc-­ in-­horses (accessed 29 May 2024). Toit, J.G. (2001). Veterinary Care of African Elephants. Novartis: Republic of South Africa. Waelbers, T., Bosmans, T., Risselada, M. et al. (2007). Inhalation anesthesia with isoflurane in a Black Jaguar (Panthera onca) for surgical repair of a fractured mandible. Vlaams Diergeneeskundig Tijdschrift 76 (2): 138–145. Washington Department of Fish and Wildlife (2022). Is your game harvest safe to consume. https://wdfw.wa.gov/hunting/requirements/ food-­safety/tagged-­game (accessed 29 May 2024). West, G., Heard, D., and Caulkett, N. (2007). Zoo Animal and Wildlife Immobilization and Anesthesia, 1e. Wiley-­Blackwell. Witz, M., Lepage, O., Lambert, C. et al. (2001). Brown bear (Ursus arctos arctos) femoral head and neck excision. Journal of Zoo and Wildlife Medicine 32 (4): 494–499. Zeiler, G.E., Rioja, E., Boucher, C., and Tordiffe, A.S.W. (2013). Anaesthetic management of two Bengal tiger (Panthera tigris tigris) cubs for fracture repair. Journal of the South African Veterinary Association 84 (1): 995. ZIMS Drug Usage Extracts for (2022). Species360 Zoological Information Management System. http://zims.Species360.org (accessed 29 May 2024).

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16 Physical Rehabilitation Kristen Hagler 1, Wendy Davies2, and Lis Conarton3 1

Circle Oak Ranch Equine and Canine Rehabilitation, Petaluma, CA, USA College of Veterinary Medicine University of Florida, Gainesville, FL, USA 3 Veterinary Medical Center of CNY, East Syracuse, NY, USA 2

Physical rehabilitation should be considered a standard option in the multimodal pain management and is a complementary treatment for the management of chronic and acute pain and the treatment of injury or illness to decrease pain and restore function. Since the 1980s, veterinary professionals have honed therapeutic treatment programs for animals by  working alongside physical therapists (PTs)  and using translational medicine to establish species-­specific treatment protocols. Specialties for veterinarians with the American Association of Veterinary Specialty Boards ­recognition (American College of Veterinary Sports Medicine and Rehabilitation, est. 2010) and a National Association of Veterinary Technicians in America recognized specialty academy for credentialed veterinary technicians (Academy of Physical Rehabilitation Veterinary Technicians, est. 2017) to further the scientific development and advancement of the science of physical rehabilitation. Therapeutic treatments prescribed focus on reducing pain and restoring or maintaining movement, management of transient or ­permanent disability using ergonomics, ­electrophysical modalities, manual therapy, and therapeutic exercise (Marcellin-­Little

et  al.  2021). Because the prevention or ­management of physical and emotional pain are priorities, other disabling conditions can become more manageable to improve the quality of life for the animal.

16.1  ­Scope of Training for the Team Therapeutic programs for animals can vary widely depending on the severity of the condition being treated, disability level, needs of the pet owner and the home environment. Some conditions may require the patient to return for frequent outpatient therapy for several weeks while other conditions may be managed with home-­based programs and intermittent follow-­up visits; however, in most cases, it means over the lifetime of the patient to reduce complications associated with a compensatory disability. When developing a rehabilitation plan, evaluating anticipated pain and the impact of a medical condition will determine the duration of treatment. It is therefore critical to evaluate the anticipated level and duration of impact to the patient and continue care throughout the duration of the condition.

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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A veterinarian who is skilled in rehabilitation therapies is fundamental to overseeing the pain management protocol and managing medical conditions. Depending on the injury, medical diagnosis, and treatments in place, the veterinarian must clearly communicate precautions and contraindications to the person(s) providing therapy and the veterinarian is ­ultimately responsible for changing the prescriptive plan regardless of who performs treatments. The veterinary team is by far the most important resource when providing rehabilitation services and while not currently required by law, it is recommended that all individuals attend one of the specialized certification programs available (see Chapter 2). These privately owned programs are available to veterinarians, credentialed veterinary technicians (CrVT)/ registered veterinary nurses (RVN), veterinary assistants (VA), and certain licensed human healthcare providers (chiropractors, physical therapists, physical therapy assistants). Professionals attain further species-­specific knowledge of anatomy and physiology, the pathophysiology of orthopedic and neurologic disease and injury, gait and functional assessment, pain management, the healing and recovery process of musculoskeletal and neurological tissues, wound healing, nursing care of non-­ ambulatory and incontinent patients, nutrition and weight loss, regenerative medicine and ­biologics, use of rehabilitation modalities, ­therapeutic exercises, and exercise prescription (Marcellin-­Little et  al.  2015). Additional training provides the reasoning behind the implementation, management, and philosophy of therapeutic modalities used and increases the success and safety of therapies being provided. Practice regulations and scope of practice for the CrVT/RVN will vary by local region. It is up to the licensed individual to follow the scope of practice regulations and the appropriate degree of supervision required by a veterinarian. As the regulatory landscape changes to  include credentialed human healthcare ­providers, the CrVT may or may not be legally

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allowed to practice with a license under such providers unless it is specifically defined in the veterinary practice act. Therefore, if the ­practice act is unclear, it is recommended for CrVTs to work under the supervision of a ­veterinarian who directs therapy. Ideally, this veterinarian has completed additional training in physical rehabilitation or is a diplomate of the American College of Veterinary Sports Medicine and Rehabilitation (ACVSMR). If this is not the case, the veterinarian is obligated to only provide therapies in which they have sufficient competency to prescribe. Advanced credentialing for CrVT/RVN’s as a Veterinary Technician Specialist (VTS) in physical rehabilitation is currently the highest specialty designation for the CrVT/RVN and is the only credential that requires the maintenance of credentials at regular intervals after successful completion of an application and examination. These exceptional individuals are considered subject matter experts in their  field of study, can carry out advanced patient management skills without coaching or prompting to successfully complete treatments, and are able to effectively communicate treatment plans to pet owners. To become a VTS (Physical Rehabilitation), applicants must contact the Academy of Physical Rehabilitation Veterinary Technicians (APRVT) and meet the minimum experience requirements, fulfill additional continuing education training, complete an exhaustive skills and knowledge list, obtain case logs with a variety of skills demonstrated, write detailed case reports, and successfully pass a competency examination. Patient case management for the CrVT/RVN varies depending on the level of education, training, and competency. In most cases, the CrVT/RVN may, just as with anesthetic management, slightly alter a patient program to address immediate or emergent needs of the patient during a treatment session. This may include adjusting the frequency or intensity of an exercise or stopping treatment if the patient is suddenly painful. The CrVT/RVN may assist the veterinarian (or other licensed team

16.2  ­The Veterinary Technician and Physical Rehabilitatio

member) by carrying out labor intensive treatments when patients are hospitalized and during outpatient treatments. They may assist the rehabilitation veterinarian (or physical therapist) with examinations, perform detailed medical record documentation, evaluate emotional health, perform extensive pet owner communication, and assess pain status, limb use, joint stability, and overall performance throughout treatments. Veterinary assistants also play an integral role in the rehabilitation team by ensuring the working environment is well prepared for the patient, assisting with therapies or disabled patients needing multiple handlers, carrying out prescribed therapies as directed, ensuring customer service needs are met, facilitating medical record coordination, and maintaining specialized equipment such as an underwater treadmill (UWTM).

16.1.1  Team Approach to Care The physical rehabilitation team includes both veterinary and human healthcare providers and it is critical for a veterinarian to directly oversee the medical needs of the patient and understand who is legally liable for the patient should injury or illness occur while under their care. PTs bring extensive expertise and knowledge to the rehabilitation team and are by far the most utilized healthcare professional. There are many ways for veterinarians to work with other licensed professionals and, depending on the structure of the rehabilitation facility (university, privately owned, nonprofit, etc.), these providers may participate in the development of treatment programs or provide specific therapies the veterinary team is unable to obtain in certification programs. Specialized training may include techniques in  joint manipulation or massage, neuro-­ physiological re-­education, wound care, orthoses, and prostheses development as well as other focused clinical areas that benefit the rehabilitation patient. The role of the PT is multifaceted and includes outlining specific functional impairments or disabilities and

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constructing a problem list, amongst other things, in conjunction with the veterinarian. They may also be in a supervisory role working with the CrVT/RVN or VA.

16.1.2  Applications in Veterinary Medicine Physical modalities such as electrical stimulation and sound wave therapy, thermotherapy, manual therapy, therapeutic exercises, aquatic therapy, and regenerative medicine are frequently utilized for animals to help the pet with support during ambulation, modification of the environment and promote improved function and recovery from an injury (Marcellin-­Little et al. 2015). Applications for patient treatment include the management of congenital malformations causing disability, advanced surgical planning for corrective procedures, nuclear medicine (electron conversion therapy), acute pain management (surgical or injury), supportive care for oncology patients, nutritional management, nursing management for critically hospitalized patients, sporting or working animal conditioning, behavioral supportive therapy (confidence and enrichment) and more.

16.2  ­The Veterinary Technician and Physical Rehabilitation 16.2.1  Common Conditions and Therapeutic Modalities Physical rehabilitation can be applied to a wide variety of medical conditions and encompasses musculoskeletal, neurological, or disabling disorders and is used for the restoration of function in the injured patient as well as in the prevention and reduction of injury in performance and working dogs. Examples of therapeutic treatment goals may include any of the following (Goldberg 2018): ●● ●●

Speed recovery from injury or surgery. Increase mobility and flexibility.

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Maintain function. Promote ideal body condition and weight. Support conditioning and endurance. Decrease pain. Enhance quality of life.

Medical conditions commonly affecting animals can be broadly grouped into the following categories: orthopedics, neurological, weight management and disablement, geriatrics, and sporting/performance and working. An even wider range of conditions may be included if disability or dysfunction is present. Conditions commonly treated are listed in Table 16.1 but are not all-­inclusive. Uncommon conditions may include recovery and support from extensive tissue trauma (e.g. burns, grafting, degloving), respiratory trauma, endocrine disorders (e.g. Cushing’s, immune-­mediated diseases),

or supportive care for oncological care and treatment. The best course when trying to determine if physical rehabilitation may benefit the patient is to determine the following: Is the patient in pain? Is the patient suffering from a disability? And is the patient’s quality of life being affected? Understanding tissue responses to injury or immobilization helps prevent further tissue damage or development of abnormal scar ­tissue once the acute stages of tissue healing have passed. Healing rates differ between bone, muscle, tendon, ligament, and cartilage, and the healing potential of these tissues are affected by disuse, immobilization, vascularity, innervation, and nutrient availability to local tissues. In most cases, too much activity in the early phases of tissue healing will cause reactivation of the injury, pain, inflammation, and in

Table 16.1  Applications of physical rehabilitation. Orthopedic Postoperative care – surgical stabilization of a joint, fracture repair, amputation, ligament or tendon repair, angular limb corrective procedures, joint replacement procedures ●● Acute and chronic soft tissue injuries – muscular, fascial, tendon, ligament or joint capsule ●● Osteoarthritis (OA) – primary or secondary ●● Developmental joint or angular limb disorders ●● Trauma and wound care ●●

Neurological Postoperative care – decompressive disc surgery, reconstructive ●● Nerve injury – central or peripheral ●● Degenerative nerve conditions (myelopathy) ●● Congenital developmental conditions (stenosis, caudal cervical malformation) ●● Syringomyelia, neoplasia, or other structural disorders (hemivertebra) ●● Secondary nerve damage from parasitological, viral, or bacterial infections (neospora, discospondylitis) ●● Balance, vestibular, cerebellar ●● Nervous system trauma (embolism, physical impact trauma, neuropathy) ●●

Other categories Pain management – acute and chronic ●● Myofascial and muscle disorders (triggerpoints, contractures) ●● Weight management ●● Cognitive support – depression, geriatric onset cognitive decline ●● Geriatric and senior care ●● Athletic and working dog conditioning and strengthening ●● Palliative care ●●

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16.2  ­The Veterinary Technician and Physical Rehabilitatio

severe circumstances failure of tissue ­structure. Whether injury to tissue is intentional (e.g. ­surgical) or accidental, a complex series of events involving many cellular and biochemical responses occurs to regenerate or repair the damaged area (Cornell 2012). Factors affecting the complexity of the cellular and biochemical response include the severity of the injury itself, whether the injury is acute or chronic in nature and the tissue type involved.

16.2.2  General Wound Healing Three phases encompass general wound healing: inflammation, proliferative (fibroblastic or reparative) and remodeling. Healing times for  each phase can slightly overlap depending on the degree of injury and specific properties of the tissues involved. The inflammatory response is present at the onset of injury and may last up to five days. It is characterized by swelling, redness, a local rise in temperature, the presence of pain, and impaired function. Therapeutic modalities applied in this stage should focus on reducing inflammation, accelerating healing and relieving pain. As tissues begin healing, they have little load-­bearing capacity and movement should be limited. This helps support the developing fibrin network, which is ­generally recognized as granulation tissue, acting as a hemostatic mechanism to eventually become the scaffold for future phases of healing. Once connective tissue has formed, a wound begins to gradually acquire tensile strength and can withstand increases in activity (Ciuperca and Bockstahler  2019). During the final phases of general wound healing, collagen fibers orient parallel to lines of stress and strain and the fibers cross-­ link in a stable formation (Liu et al. 1995). It may take up to two (2) to three (3) weeks after injury for collagen to reach a maximal deposition point and tensile strength continues to progressively increase over the course of approximately one (1) year (Henderson and Millis 2014).

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16.2.3  Bone Bone is one of the few tissues that can undergo direct cellular restoration to achieve 100% of the original biochemical properties; however, if the endosteal vascular supply is severely disrupted or fracture management is delayed, restorative healing can become compromised. In healthy individuals, bone mineral homeostasis is maintained between bone resorption and deposition as well as continuous remodeling secondary to mechanical stresses, adapting to the forces under which it is placed “Wolff’s law” (Styles and Einhorn  1997). During the inflammatory phase, the goals are to reduce pain and soft tissue inflammation, and maintain joint health and range of motion (ROM). Patients can be guided through ­controlled mobility, depending on the fracture stability with careful implementation of rehabilitation therapies; however, if the mechanical load exceeds the strength of tissues, refracture or inhibition of bone healing may occur and cause disruption to extraosseous blood supply formation. In the reparative phases, brief and gradual increasing of cyclic loading may occur to initiate micromotion and improve callous formation, with a continued focus on the maintenance of joint health through active or passive range of motion (PROM) therapies (Doyle 2004).

16.2.4  Muscle Injury to muscle occurs because of lacerations, contusions, ruptures, ischemia, and strains. The degree of injury correlates to the intensity and duration of the tensile load applied to tissues, and healing times are determined by strain grading (1–4). Injury to the muscle or tendon typically occurs at the muscle-­tendon junction. Clinical grading ­systems have changed significantly over the years and currently combine detailed Magnetic Resonance Imaging (MRI) and ultrasound imaging with clinical presentation to determine severity grade, prognosis,

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and management (Grassi et al. 2016). The systems that combine such features include the Munich Muscle Injury Classification (2012), the Italian Society of Muscle Ligament and Tendon Classification (2013), and the British Athletic Classification (2014). Muscle strains may be acute or chronic; the degree of damage to the muscle results in varying degrees of tearing to the muscle fibers and supporting connective tissue. Healing of muscle tissue follows that of general tissue healing phases, however the reparative phase is a competitive process between regeneration of functional myofibrils or production of fibrous scar tissue depending on the severity of the injury and muscle gap size therefore, mobility should not begin until healing is well underway (Caplan 1991). When motion is excessive, the muscle will heal with more fibrous scar tissue as the injury gap widens. In cases of muscle or limb injury where disuse occurs, atrophy sets in very quickly. Type I muscle fibers involved with postural function, extensor muscles, and those that cross a single joint are especially susceptible to atrophy when not used. If direct trauma has not occurred but muscles are affected by disuse, such as with hospitalization, rehabilitation therapies can be targeted toward restoring or maintaining muscle fiber length and sarcomere distribution while minimizing the formation of scar tissue. Muscle atrophy can be attenuated in recumbent patients with assisted standing therapy for up to ten (10) minutes total per day by approximately twenty-­five (25) percent (Bockstahler et  al.  2004) and performing PROM exercises to the peripheral joints can help maintain overall synovial joint and muscle nutrient health to reduce pain. When muscles are immobilized, chronic load and strength decrease rapidly in the first week, with further losses occurring more gradually over time. Depending on the immobilization position of the muscle, atrophy and fiber length are affected, which leads to increased muscle stiffness resulting from increased ­connective tissues. Other conditions that lead to muscle atrophy include geriatric onset

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sarcopenia, muscle deinnervation or neurogenic atrophy, and endogenous and exogenous c­ orticosteroid administration.

16.2.5  Tendons and Ligaments Disruption to tendinous and ligamentous structures carry special considerations for rehabilitation due to unique biochemical makeup, tensile properties, and location. Healing tendons follow the general phases of tissue healing during the inflammatory phase; however, extensive timelines occur during the repair and remodeling phases. During tendon repair, the goal of treatment is to minimize adhesions and maximize the return of function. This is typically achieved through surgical intervention and may require a minimum of twenty-­eight (28) days for collagen deposition and alignment of fibers parallel to the lines of stress. Strength of tendons after injury retain only seventy-­nine (79) percent of original tensile strength one (1) year following injury (Dueland and Quenin  1980), which makes remobilization of tendons a prolonged process with careful reintroduction of activity. Conservative exercise with light weight bearing may begin at six (6) weeks after repair because having twenty-­five to fifty percent (25–50%) of normal tensile strength is con­ sidered adequate for withstanding normal ­muscle force. A minimum of twelve (12) weeks of restricted activity for more active loading, including light exercise to maintain ROM and stimulate healing callus cells, is recommended (Henderson and Millis 2014). Ligament healing and rehabilitative measures are largely unanswered because ligaments heal differently depending on the location. Inflammatory phases are characterized by an organized hematoma to fill the defect with a subsequent influx of inflammatory cells. The reparative phase may last approximately six (6) weeks, and in the final stages, may take more than twelve (12) months. Ligament strength may only be fifty (50) to seventy (70) percent of the original tensile strength (Frank 1991) with sprain-­avulsion fractures at the ligament-­bone interface having the best prognosis for return

16.3  ­Client Communication and Activity Modificatio

to normal tensile strength in two (2) to four (4) months. Rehabilitation implementation timing can vary widely depending on the ligament involved and from one study in horses, implementing a low-­duration (30-­minute) high ­frequency (6 days a week) exercise program demonstrated the greatest benefit to ligament strength (Cherdchutham et al. 2001).

16.2.6  Articular Cartilage Cartilage tissue is primarily avascular and without lymphatics and when damaged is directly related to the type of trauma incurred, which severely limits repair. Normal joints require loading and unloading to maintain health, which is approximately seventy (70) to eighty (80) percent water by weight with the remainder composed of proteoglycan aggregates and chondrocytes. A capsule surrounding the joint facilitates hydrostatic lubrication of intra-­articular surfaces during weight bearing, which also provides cartilage nutrition. Without hydrostatic lubrication from weight bearing, cartilage matrix synthesis decreases and diffusion of the cellular components within the synovial fluid is not disseminated, leading to decreased joint elasticity and changes in mechanical loading abilities. If cartilage suffers from pressure necrosis, overload or direct injury cartilage surfaces begin to fissure and lose the ability to distribute load onto subchondral bone. Acute management of cartilage injury includes debridement of loose fragments if present, and if damage is the result of joint incongruity, early implementation rehabilitation to promote joint health can help improve circulation and reduce adhesion development long term.

16.3  ­Client Communication and Activity Modification Credentialed veterinary technicians play key roles in directly working with pet owners on how to manage the needs of a patient with limited mobility, possibly more so than any other

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clinician involved in the medical management of patients with neurologic injury or disease (Sims et  al.  2015). They provide guidance regarding pain management, quality of life assessment, environmental modifications, use of assistive devices, ensure therapeutic plans are effectively communicated and act as a patient advocate when pet owners require additional guidance. Pet owners are an integral part of the team and communication is paramount for rehabilitation to be a successful intervention in managing pain. Understanding the pet’s diagnosis, including potential areas of complications from recommended treatments, is part of pet owner education. Treatment programs should be designed so that pet owners can be active participants in the home care program. In some instances, pet owners may be unable to execute a recommended treatment, which can lead to perceived treatment failure. Useful guides such as detailed disability, mobility, behavior, and pain questionnaires can be utilized by the rehabilitation team to assess the needs or limitations of the family and are detailed in Section  16.4. Home care program education can include environment modifications, assistive tools to augment existing or predicted disability, and detailed plans for home exercises or manual therapy (see Section  16.4). These instructions should be delivered with at least two methods of communication (written and oral); and when the appropriate reciprocal demonstration of a therapy should be performed by the pet owner with regular intervals (every four weeks) of follow-­up. One of the greatest reasons for home care program noncompliance or failure is pet owner fear of hurting their pet. Pet owners working closely with the CrVT can build a trusting relationship and feel more empowered when carrying out home therapies for successful pain management and home care plan delivery. Modification of activity, when an animal is in pain, prevents the development of abnormal pain experiences, further disability, or compensation, and provides protection against ­surgical complications or failure. Aside from

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standard postoperative activity restriction guidelines, which typically include at minimum fourteen (14) days of convalescence for soft tissue structures to heal, certain conditions may require additional modification. Current patient joint motion angles, muscling, pro­ prioception, balance, conditioning, pain (or ­potential for pain), life stage, and disability level are considered when setting activity goals. Therapists should consider a gradual reintroduction of activity once released by surgical services, increasing fifteen to twenty (15–20%) percent weekly until previous activity goals are met for patients who normally engage in strenuous exercise to prevent overuse injury not associated with a surgical procedure. Aging patients will take much longer to recover after a surgical procedure and on some occasions, may develop additional weaknesses secondary to being manipulated during anesthesia and upon recovery due to the influence of sedatives and analgesics. Modifications for patients with progressive disease such as osteoarthritis (OA) or degenerative neurological conditions attempt to prevent falls and overuse injury. It is common to recommend a low-­ impact lifestyle with minimal off-­leash running, jumping, and hard turning activities; to avoid stairs whenever possible; help getting in or out of vehicles; adhere to a high-­frequency and low-­duration exercise routine; and implement early intervention strategies for long-­ term joint health, including supplementation and weight management.

16.4  ­Patient Assessment 16.4.1  Veterinary Diagnosis – The Rehabilitation Team The patient’s ability to perform daily tasks is given the highest priority and results in a functional emphasis rather than a medical diagnostic or pathological focus on evaluation and treatment. A model described by the World Health Organization’s International Classification of

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Impairments, Disabilities, and Handicaps (ICIDH) (World Health Organization  1997) defines the following terms pertinent to the implementation of the disablement model in practice: active pathology, impairment, functional limitation, and disability. Using these definitions, practitioners can select therapeutic modalities and interventions appropriate for the management of the patient over the course of care. A veterinary rehabilitation examination is highly detailed and includes additional evaluation parameters when compared to standard clinical, orthopedic, and neurological exami­ nations. Medical history including signalment (age, breed, gender, and age of alteration), nutrition and body condition scoring, allergies, ­disease control measures (e.g. vaccination ­status), previous injury, and known trauma are con­sidered standard for inclusion. Some patients have occupational requirements (working and performance animals), are living in a challenging home environment, or have prior emotional health history that may affect overall outcome of treatment planning. The description of the presenting ­complaint should include the duration of the injury, its effect on the patient, previously attempted treatments and the outcome, the overall impression by the  owner regarding the progression of the ­disease, the effect of ­physical activity including fatigue on the patient, and any physical documentation of the patient in the home environment that may affect ­con­dition management. Veterinary diagnosis may be achieved through physical examination, ­radiography, serological testing, and clinical presentation; however, in the complicated case presentation, patients may require advanced imaging such as MRI, computed tomography, electromyography, fluoroscopy, or musculoskeletal ultrasound to achieve an accurate clinical diagnosis. In some cases, arthrocentesis may be required to rule out auto-­immune dysfunction or inflammatory disease. To account for the ­varied requirements for recovery from surgery or illness and ­management of the function, examinations ­utilize multiparameter collection methods. This includes objective measurement

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tools, joint stability and quality of motion, integrity and strength of soft tissues, structural and ­postural analysis in static and dynamic motion, gait analysis, level of ­disability, and pain scoring.

16.4.2  Objective Outcomes: Goniometry and Muscle Girth Measurable outcomes such as goniometry and muscle girth measurements can be used to assess patient progress and help determine treatment plan effectiveness. Findings are used to adjust therapeutic goals, therapeutic exercise type, repetition, duration, and frequency. Goniometric measurements are achieved by using a joint angle measuring device called a goniometer. The two arms of the goniometer are placed along the bones immediately proximal and distal to the joint being examined. The two arms of the goniometer are then lined up with specific anatomical landmarks for each joint with movement measured in both flexion and extension (Norkin and White  1995). In some joints, (a)

valgus and varus are included. Angle measurements can be affected by pain or initiation of the muscle flexor response in response to pain, and in these cases, only the comfortable ROM is assessed. To obtain reliable, reproducible measurements, joint angle measurements are repeated three times and the mean is obtained. As measurements are taken, joints are simultaneously assessed for crepitus, pain, and dynamic instability during movement (Millis et  al.  2004). Jaegger reported normal ROM (degrees) for appendicular joints in healthy Labrador Retrievers (Jaegger et  al.  2002) and may be used as a diagnostic predictor of joint function. The fulcrum of the goniometer is typically placed over the center of the joint while the proximal base arm (without the angle measurements) is kept stationary. The motion arm of the goniometer is lined up with landmarks of the limb and the distal aspect of the joint is flexed and extended to obtain joint angles. Appendix 16.A summarizes additional techniques for other joints and stifle goniometry is depicted in Figure 16.1. (b)

Figure 16.1  (a,b) Step 1: The goniometer fulcrum is placed near the lateral femoral condyle. Step 2: The base arm follows the long axis of the tibial shaft to the lateral malleolus. Step 3: The other arm follows a line to the greater trochanter along the lateral femoral condyle. Normal flexion angle is 41° and extension is 162°.

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Limb circumference measurements are an indirect method of assessing changes in muscle mass and assessing the overall changes with increases or decreases in strength. Using a no stretch, retractable spring-­loaded tension tape device (Gulick II), muscular regions commonly affected by orthopedic and neurological disease can be evaluated to determine how well a patient is responding to treatment. Muscle circumference should be the mean of three measurements with the following regions evaluated bilaterally: gluteal and quadricep (Figure 16.2), thigh girth at 70% of femoral length (Figure  16.3), deltoids (Figure  16.4), triceps (Figure  16.5), and the flexor/extensor musculatures of the antebrachium (Figure 16.6). Appendix 16.B describes techniques for obtaining muscle girth.

(a)

(b)

16.4.3  Pain and Disability Scoring – Methodology in Pain Scoring and Assessment Pain assessments occur prior to starting rehabilitation to prevent exacerbation of injury and  to further localize painful regions. To

Figure 16.2  Gluteal and quadriceps thigh circumference. The tape measure device is placed snugly in the groin and wrapped to the lateral aspect of the thigh, meeting at the greater trochanter (Sprague 2018 / with permission of John Wiley & Sons).

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Figure 16.3  (a,b) Muscle girth −70% thigh circumference. Limb position should be at a neutral angle and not in full extension or flexion, causing muscle mass girth to change secondary to approximation or elongation (Millis et al. 2004). Step 1: Thigh length by measuring from the tip of the greater trochanter to the distal aspect of the lateral fabella. Step 2: Circumference is determined at points equal to 70% of the thigh length beginning with the most proximal location.

effectively manage pain in animals, validated methods to measure pain are utilized whenever possible. Instruments that can both monitor pain and provide repeatable and reliable data have been developed to assist practitioners in veterinary medicine (Reid et  al.  2018). One objective method includes gait analysis. This evaluates the animal in real-­time motion and detects subtle differences in weight bearing between the limbs. This can include force plate walkways, kinematic and kinetic gait analysis, pressure-­sensing walkways, activity monitors, and accelerometers. Another objective method utilizes physiologic biomarkers. These tools measure direct pain biosignals (paintrace.com)

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Figure 16.6  Flexor and extensor muscles of the antebrachium circumference. Around 20% percent inferior of the distance from the tip of the olecranon to the distal end of the styloid process of the ulna. Evaluates the proximal flexor and extensor musculatures.

Figure 16.4  Deltoideus (shoulder) circumference. The tape measure is placed snugly in the axilla and wrapped to meet at the lateral aspect using the acromion process on the scapula as a landmark.

Figure 16.5  Triceps circumference. At a point above the lateral epicondyle of the humerus where the triceps muscle group transitions into the tendon inserting onto the olecranon process of the ulna.

to identify the presence and intensity of pain depending on the markers being evaluated. Depending on the equipment, markers may include stress, hormonal, and metabolic changes; biochemical analytes, or inflammatory mediators. However, many of these biomarkers and biosignal tools are still under development and do not have robust studies validating their efficacy or sensitivity.

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The most utilized method of pain detection in animals is a multiparameter subjective measurement system. This system includes the ­veterinarian examination, clinical observation of the patient in motion and during Daily Activities of Living (DAL) in conjunction with Clinical Measurement Instruments (CMIs), and observation-­based owner questionnaires evaluating activities of daily quality of living, pain, and disability can be scored. CMIs are used to assess chronic pain and help to ameliorate the challenges in using pet owner recall of information alone. Questionnaires for pet owners, which have been validated, include the Canine Brief Pain Indexⓒ (CPBI) developed by Dr. Dorothy Cimino Brown and the University of Liverpool – Liverpool Osteoarthritis in Dogs (LOAD) and are preferred when used as tools to  assess pain and response to rehabilitation ­treatment at each visit. Other systems are also utilized but are not validated and should be used thoughtfully. A Visual Analog Scale (VAS) using a 100 mm (10 cm) line numbered zero (0), no pain, up to ten (10), the worst pain possible, can be used to represent the pain perceived by  the animal. This method is not validated, but it does provide a semiquantitative method to assess pain and pain trends over time (Wiese 2015). Gait analysis can provide the veterinary team with large amounts of information regarding patient overall comfort in the

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clinical and home environments. Gait is scored in both the walking and trotting (if the patient is able) speeds while postural movement is often observed in static and patient-­guided movements. Pain invokes abnormalities and can then be confirmed through physical palpation during an examination. These observations can provide a concrete way to evaluate initial pain experiences and over time if exercise and treatments prescribed are working.

16.4.4  The Musculoskeletal System Musculoskeletal disease changes the way an animal functions and includes adaptive and compensatory mechanisms, which constitute both joint and muscular levels in thoracic and pelvic limbs (Stark et al. 2021). An element of adaptation includes the neurologic system, which manifests as central pattern generators, reflexes, and higher locomotion centers depending on how neuronal circuitry is involved. A study by Stark et al. (2021), demonstrated the importance of analyzing body size, structure, and dexterity in dogs while including diseased states to determine joint control and loading in the dog during locomotion. As models continue to be developed and are supported with evidence-­based research, understanding factors making up the musculoskeletal system, including normalcy for specific breeds and ages, and abnormalities that may affect their overall system and functioning improves pathology recognition and successful implementation of treatments. Determining where pain originates from relies on a thorough understanding of the anatomy and function of muscle, tendons, ­ligaments, fascia, and joint function during movement. Joints have both a concave and convex surface that allows them to glide over one another as the joint moves through ROM. When pain is present, ROM can be decreased due to several reasons including osteoarthritis, tight muscles, avulsions or tears to ligaments, tendons, or fascial adhesions. The role of the CrVT in musculoskeletal

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e­ xaminations is to assist the veterinarian in narrowing down the cause of pain using observational skills during animal handling. There are three (3) main types of muscle in the body: skeletal, smooth, and cardiac. Skeletal muscles attach to bones and are responsible for movement. They are controlled by the peripheral nervous system (PNS) and are under voluntary control. Smooth muscles are within internal organs, the gastrointestinal tract, bladder, and the uterus. All these muscles are controlled by the autonomic nervous system (ANS) and therefore cannot be controlled voluntarily. Finally, cardiac muscle composes the heart and is under the control of the ANS. For the purposes of this chapter, skeletal muscles and their relevance to movement will be focused on. Skeletal muscles can be organized into primary movers and secondary movers (Riegger-­ Krugh et al. 2014). Primary muscles responsible for normal physical movement are usually larger and cross over joints to allow a full ROM. Secondary movers are much smaller and contribute to the primary movers’ ability to move the body. Muscles classified as ­anti-­gravity are those that allow an animal to remain in an upright, weight-­bearing position. The triceps muscle is an example of an anti-­ gravity muscle. Stabilizer muscles are those that keep the animal steady while another muscle moves a joint. Together, stabilizer and anti-­gravity muscles allow an animal to stay upright when moving and maintain balance when standing still. The role muscles play in movement and how they can become painful or injured is dependent on the muscle contraction type; isometric or isotonic. Isometric muscle movement is a force generating contraction that does not change the length of a muscle and is not associated with any movement of a body part. It is difficult to reproduce in animals and  is not utilized in physical rehabilitation. Isotonic exercise includes eccentric and concentric muscle contractions and occurs through partial or full ROM, while a constant

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tension in a ­muscle is maintained as the muscle length changes. When a muscle contracts while lengthening from a shortened position, the contraction is eccentric. This isotonic exercise results in the lengthening of a muscle while creating a force (or is under constant load throughout a ROM). Concentric muscle contractions are a type of isotonic exercise that results in the shortening of a muscle from a lengthened position during movement, such as when humans perform forearm curls. The contraction of the biceps occurs, shortening the muscle, which results in the raising of the barbell. Eccentric contraction occurs when the barbell is lowered from the raised position as the elbow is extended, lengthening the muscle while under a force load. Flexion of a muscle generally results in the bending of a distal segment around a joint and results in the bones getting closer together to create a smaller angle. Muscle extension, on the other hand, results in a limb extending away from the body with an increasingly larger joint angle generally not to exceed 180°. Understanding what happens to muscles as  they engage in movement and how they are  utilized for motion allows rehabilitation ­practitioners to prescribe specific exercises for muscle strengthening and conditioning. Muscles cannot function at the same rate indefinitely. They rapidly atrophy when not exercised and are susceptible to aging or systemic disease, making regular exercise programs critical for maintaining conditioning levels. When a muscle can no longer maintain strength during a contraction it becomes fatigued and becomes susceptible to injury. During muscle fatigue, cells are no longer able to balance adenosine triphosphate (ATP) production and consumption (Millard 2014) and become deficient. Increases in ATP are needed during muscle exercise and if the ATP can no longer be replenished, energy is depleted. This deficiency causes muscle fatigue and the ­inability to contract however with targeted muscle conditioning, fatigue can be attenuated. Using the overload principle during

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conditioning, muscles are pushed slightly beyond cellular and strength levels to facilitate ­adaptation to new exercise conditions and ultimately improve performance and reduce injury. Exercise programs for conditioning, strengthening, and endurance must model the activity type muscles will be exposed to in order to benefit from training adaptations. For example, if the sport is long distance racing, a conditioning program would include exercises to improve endurance such as trotting, r­ unning, or swimming. Muscles rely on nerve impulses for ­voluntary action and are susceptible to degeneration, traumatic injury, denervation, or neurogenic atrophy. A contraction occurs when nerves innervate a muscle and when disrupted, various types of muscle dysfunction can occur. One motor neuron can innervate numerous muscle fibers, referred to as a motor unit, and multiple motor units are needed to contract an entire muscle (Gillette and Dale  2014). When disease or destruction affects the nerves, those muscles can cease to function normally and cause varying levels of disability, lameness, and muscle tone. When a muscle involuntarily contracts and  will  not relax, this is known as a spasm. The ­animal will often be visibly uncomfortable and  may show an obvious lameness. Muscle spasms can be due to overuse, dehydration, or ­maintaining the same position for an extended period of time (Dragone et al. 2014) and can be resolved through therapeutic massage, myofascial release, or in some cases electrotherapeutic modalities are needed for resolution. In neurologic disease such as IVDD, impulses sent from the brain to signal nerves innervating the motor units are disrupted and depending on the severity of disruption, is called a root signature when motor movement is impaired. When nerves are compressed or destroyed, signals are not transmitted to the muscles well causing flaccidity or hypertonicity depending on where a spinal lesion is located. Muscle tonicity is considered the amount of tension in a relaxed muscle and helps differentiate between upper motor neuron (UMN) or lower motor neuron (LMN) disease.

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Muscle tone, especially that of the extensor muscles, can be evaluated through passive manipulation of the limb (Bartner  2020) and is characterized as flaccid or spastic. When a muscle is flaccid, there is little to no tone and is characteristic of LMN disease. Typically, the limb is limp or has very little voluntary motor movement, often dragging along as the animal attempts to ambulate. Muscles that are spastic or hypertonic are stiff and are difficult to flex, which is characteristic of UMN disease; however, normal muscle tone can also be present in these patients. Active joint ROM is more pronounced during movement and joints typically do not engage in the full available motion because muscles are receiving impulses to activate too early. Neurogenic atrophy occurs quickly when motor units are not communicating with damaged nerves and is more profound and  quicker to happen than disuse atrophy from orthopedic disease, which can take weeks to months.

16.4.5  Structural and Postural Evaluation Postural evaluations, or how an animal prefers to stand, sit, lie down, and perform DAL ­without assistance, plays an important role in physical rehabilitation plan development and evaluation. When dysfunction is present, ­animals will shift body weight and develop compensatory postures (Figure 16.7) to avoid certain positions that cause additional joint loading and subsequent pain. The severity of compensatory postures can be determined through discussions with the owner about how successful their pet is at home when performing activities. During the clinical assessment, team members can observe the animal’s ability to move freely around the examination or treatment area. Areas of subjective observation include conformation and posture, stance and sit position, transitions between postures, the ability to hold a posture, and response to varied flooring textures. It should be noted how long a patient is able to stay standing or if they prefer to lie down or sit. Appendix 16.C: Postural Compensations

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Figure 16.7  Patient sitting and exhibiting compensatory postures in the thoracic and pelvic limbs. The right elbow is externally abducted, and the paw is medially rotated. The left thoracic limb is overly centered under the shoulder. The pelvic limbs are positioned in a “splayed” or “sloppy” sit. This patient has been diagnosed with chronic elbow, stifle, and hip joint disease. Courtesy of Johanna L. Hagler.

and Associated Medical Conditions outlines common assessment parameters. The appendicular skeleton includes the thoracic and pelvic limbs, and the axial skeleton includes the spine, including the tail. The thoracic limbs, apart from chondrodystrophic breeds, bear nearly sixty percent (60%) percent of the total body weight. The dog’s center of gravity is located at the mid-­chest level behind the scapula and when injured, the center of gravity is shifted to other less affected areas, causing varying degrees of lameness to occur (Gross 2002). The pelvic limbs of the dog bear nearly forty (40%) percent of the total body weight and are designed to provide propulsion and directional changes while on level surfaces and “drive” the cranial portions of the body forward during activity. Differences in angulation occur between breeds and canine patients with an upright or straight pelvic limb conformation may be at higher risk for stifle injury due to a lower surface area for muscular attachments compared to an evenly balanced structure.

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Figure 16.8  Momentary three-­leg standing can evaluate overall strength and compensatory tendencies. Evaluators observe for shifting of the other weightbearing limbs, head, and tail position changes during balancing. Average strength for healthy animals is between 15 and 20 seconds. Courtesy of Johanna L. Hagler.

When evaluating strength and posture, a limb may be unloaded momentarily while the patient stands on a level surface, which causes momentary weight bearing on three legs (Figure 16.8). Evaluators are assessing preferences for weight distribution and if the animal compensates when not on four legs. Picking up an affected limb should be relatively easy, while picking up the unaffected limb is difficult because the animal is relying on that limb for support. Animals who are successfully able to balance on three (3) legs easily may be tested further through diagonal leg testing, which challenges momentary balancing abilities on the diagonal limbs. When evaluating the fore or rear limbs for posture and structure, examiners should evaluate bilaterally in order to detect subtle differences between the contralateral limbs.

16.4.6  Gait Analysis and Movement Four (4) main gaits are used by the dog: the walk, trot, canter, and gallop (Zink  2013); ­however, only three (3) are utilized for gait analysis. When gaiting, the most accurate analysis of movement will come in a controlled environment without evident distraction. Orthopedic gait evaluations are often limited to the walk, trot, or amble because of pain.

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However, patients should be evaluated at two different gaits when possible. The most efficient gait is the trot, a two-­beat gait, and occurs when the diagonal front and rear limbs move forward, striking the ground at the same time. This gait is best in determining lameness because the fore and pelvic limbs are never assisted in bearing weight by the contralateral limb. It is also slow enough for an experienced human eye to observe stride length and foot placement for most breeds. The walking or ambling gait commonly utilized by animals is the slowest and only gait with moments of three (3) feet on the ground simultaneously. Ambling occurs when a dog is walking and begins to speed up gradually and occurs when animals are tired but want to move more quickly. This gait appears as if both limbs on the same side of the body are moving together but if there are moments with three (3) feet on the ground, it is considered a fast walk and is normal. A gait commonly confused with the amble is called the pace. The pacing gait is seen as the animal gradually speeds up but doesn’t transition to a trot. Both limbs on the same side of the body move forward together so that there are only two (2) feet on the ground and is followed by a period of suspension. The pace is very inefficient, with the center of gravity moving from side to side wasting efforts centering the body instead of moving forward. Figure 16.9: GAIT ANALYSIS – WALK, TROT, PACE visually depicts overall limb movement.

16.4.7  Lameness A validated scoring system is best utilized however in some literature, intra-­observer reliability may improve using a VAS using a ten-­ centimeter (10 cm/3.93  in.) line for observers to make a mark on the line indicating degree of lameness from sound to non-­weight-­bearing. Other numerical scoring systems (NRS) assign numerical values to a lameness for at least two gaits independently for finer discrimination of gait analysis. Subjective scoring systems cannot replace objective force plate or kinematic gait analysis but if observers agree on a grading

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Walk or Amble

Diagonal trot

Pacing

Figure 16.9  Three (3) gaits commonly utilized during gait analysis: the walk or amble (three beat gait), diagonal trot (two beat gait), and pacing (a two-­beat lateral gait). Courtesy of Johanna L. Hagler. Table 16.2  Lameness numerical rating (NRS) scale. Numerical score

Lameness description

0

Walks normally

1

Slight lameness

2

Obvious lameness

3

Severe weight-­bearing lameness

4

Intermittent non-­weight-­bearing lameness

5

Continuous non-­weight-­bearing lameness

system for lameness scoring assessment, the NRS and VAS can reliably be used between observers. When using an NRS, numbers start at zero (0) with the animal walking normally and  end at five (5), indicating continuous ­non-­weight-­bearing lameness (Table 16.2) (Lameness Numerical Rating Scale). Lameness scores are assigned for the walk and trot individually (Gross-­Saunders et al. 2014). Lameness characteristics in a thoracic limb produce a brisk vertical head bob as the affected limb strikes the ground resulting from attempts to shift weight off of the affected limb to the opposite end of the body. In contrast, hindlimb lameness causes a pronounced head bob downward as the affected limb strikes the ground, shifting weight cranially. Animals with pelvic limb lameness also tend to keep the head lower at shoulder height and may have a hip hike with the affected rear limb, trying to tilt the pelvis away and lessen ground reaction

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forces as the limb strikes the ground. Determining lameness in bilateral or contralateral joint conditions may require various speeds of gait, directional changes to elicit a lameness or videography (which can be slowed down by frames) to determine affected limbs. Spine position, joint motion, stride length, limb carriage during swing (the non-­weight bearing) phase and response to varied surfaces should also be noted by evaluators during lameness evaluations. Animals with bilateral forelimb and hindlimb lameness are significantly more difficult to assess and may exhibit a “double” head bob and if the pelvic limbs are affected, a hopping motion. In the thoracic limbs, stride reach or protraction with the shoulders and elbows may be concurrently assessed to help differentiate if one limb is more affected than the other. In all cases, neurological disease must be considered as a possibility because some conditions can mimic orthopedic disease (Zink 2013). In addition to the VAS and perhaps more reliable, a questionnaire may be used for mild to moderate lameness in the canine. Using one study (Hudson et al. 2004) responses to questions recorded on a standard 10-­point VAS had a significant correlation with ground reaction forces, including how often the dog gets exercise, stiffness when rising in the beginning and end of the day, lameness when walking, and willingness to play. Another evaluation tool helping to correlate lameness with ground reaction forces is the Helsinki Chronic Pain Index. This system found mood, play, locomotion while walking and trotting, getting up,

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and difficulty moving after major activity to be valuable in helping identify dysfunction with OA (Hielm-­Bjorkman et al. 2003).

16.4.8  The Aging Patient Aging is a decline in reserve strength that normally assists with recovery and changes in all body systems, which increases the likelihood of developing a disease. It is also a term that refers to a complex set of biological changes that result in a progressive reduction of the ability to maintain homeostasis when exposed to internal physiologic and external environmental stresses (Goldston  1995; Bellows et  al.  2015). These changes ultimately lead to decreased vitality, increased vulnerability to disease, and eventually death. Older animals should continually be evaluated for the development of concurrent diseases such as degenerative joint disease, neoplasia, endocrine disorders, and obesity. The attenuation of muscle atrophy, pre­ servation of joint function maintenance and support of psychological well-­being are primary goals for the aging patient. Aging ­animals are susceptible to sarcopenia, the loss of muscle mass due to degeneration with age and has been confirmed in a study of Labrador Retrievers (Hutchinson et  al.  2012). Muscle fibers have a decreased number and size and have a reduced responsiveness to exercise. While most aging pets do not need to be active for long periods of time, they do require endurance to perform activities ­specific to their social requirements. Low-­duration, high-­ frequency exercise should be implemented on a regular basis for the most consistent gains, and if implementing therapeutic exercises, repetition number and  assistance needs should be individualized according to the animal’s capabilities. Exercises should promote normal daily life activities such as grooming, eating, drinking, and elimination with independence and proper posture. Normal functional movements like sitting, standing, turning around, and backing up change with

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age and should be constantly evaluated for decline. Environmental modifications for aging animals are often more pronounced and may include assistive devices like support harness systems or slings and flooring changes to reduce slipping. Cognitive fitness is an often-­overlooked aspect of aging for both humans and animals. It becomes easy to attribute changes in cognition to age as older pets sleep more, ignore previous learned behaviors, become more irritable or have a change in bathroom habits. Sleeping requirements change for some animals with low physical fitness because the efforts of routine daily activity become challenging, and they can become exhausted by the end of the day. Cognitive dysfunction syndrome (CDS), which is based on the recognition of behavioral changes and exclusion of other medical conditions, should also be considered in the aging patient. Animals with CDS may be disorientated on occasion, have altered social interactions, varied wake–sleep cycles, repetitive behaviors, or pacing, become stuck in corners, have changes in elimination habits and activity as well as increased anxiety. Accurate diagnosis of CDS can be difficult because changes in behavior are the first or only indicators of pain and illness, making medical monitoring crucial.

16.5  ­Patient Management 16.5.1  Assistive Devices: Mobility Wheelchairs, Harnesses, and Footwear Assistive technology is an umbrella term that includes assistive, adaptive, and rehabilitative devices for individuals with disabilities and includes the process used in selecting, locating, and using them. Assistive technology can be defined as “any item, piece of equipment, or product system, whether acquired commercially off the shelf, modified, or customized, that is used to increase, maintain, or improve functional capabilities of individuals with

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disabilities” (Nicolson et al. 2012). Determining what a patient needs is determined by the type of injury, chronic condition being treated, level of independence or need for assistance, prevention of further injury based on envi­ ronment, and therapeutic or activity goals. Animals may require the aid of an assistive device for a variety of reasons ranging from temporary postsurgical recovery, weakness secondary to age, and during activities carrying certain physical risk (e.g. hiking, swimming). The handler’s ability to don the assistive device is also taken into consideration when choosing an appropriate assistive device design because if they cannot place it on the patient, it will be ineffective or not utilized. Equipment can include harnesses, protective footing, traction aids, and mobility wheelchair carts. Some products serve a specific function, focus on a particular activity, or provide ­comfort and ­leisure. Thousands of products exist, which may lead to overspending and inappropriate product choice, use, or size for the intended use. Therapists can help guide pet owners through the marketplace, avoid costly overstocking, and address the patient’s individual needs. Wheelchairs can offer patients freedom of movement and can improve quality of life. Whether suffering from a neurologic condition, amputation of an appendage, or suffering from severe OA, the addition of a wheelchair can help relieve pain during mobility and increase the psychological wellbeing of the patient. There are many options, and it is very important to ensure an appropriate fit (Figure 16.10) so as not to cause wounds or compensatory muscle soreness due to an ill-­fitting cart. There are several pet wheelchair companies, and each company has specific instructions on how to measure for the appropriately sized cart based on patient measurements, activity goals and fabrication techniques. Table 16.3 provides possible resources for equipment. When used short term, a lightweight simply designed abdomen sling style harness is the  most appropriate. Long-­term use often encompasses disabled patients who require

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Figure 16.10  Ideal body posture for a dog with pelvic weakness using a mobility cart. The patient’s topline (spine) should be in a neutral position (not bowed or curved) and the saddle should support the pelvis, so the rear legs are positioned in a neutral standing position. The yoke is positioned over the shoulders for comfort and wheel axle location may be altered (variable, neutral or counter-­balanced) to support varying levels of weakness. Courtesy of Johanna L. Hagler. Table 16.3  Mobility carts. Company name

Fabrication style

Eddie’s Wheels™

Full custom Front end, rear end, quad cart options

Doggon’Wheels

Partially adjustable Front end, rear end, quad options

K9 Carts

Partially adjustable Front end, rear end, quad options

Walkn’ Wheels®

Fully adjustable Front end, rear end, quad options

significantly more physical assistance because of permanent or progressive disability. When choosing a harness, professionals should consider harness handle placement and patient needs. While abdomen sling-­style harnesses are useful, they produce vertical lift against the abdominal region, including the bladder, and lumbar spine. The most ideal location for a handle is near the thoraco-­lumbar junction just behind a dog’s center of gravity, behind

16.5 ­Patient Managemen

Table 16.4  Assistive devices.

Figure 16.11  Two-­point harness system providing support for the thoracic and pelvic limbs. Courtesy of Johanna L. Hagler.

the shoulder blades to distribute vertical forces. Animals with an even higher degree of disability or amputation of a limb may require assistance from two lift points over the shoulders and hips (Figure 16.11). The lift point for the pelvic limbs is directly under the pelvic region because the sacrum helps distribute pressure points and in thoracic limbs, the sternum provides the lift point. Using a supportive harness helps patients with motor function to be assisted in motions necessary to prevent falls as well as providing the benefits of gait repatterning and strengthening (McDonald and Sadowsky 2002). In addition to handle locations, slings and harnesses can be fitted for the forelimbs, hindlimbs, or both. They should have long, hand-­held straps attached to allow proper body mechanics to avoid personal injury to the handler when supporting the pet (Goldberg and Tomlinson  2018). An assistive harness should not obstruct general movement, specific limb movement, or impede normal ­urination or bowl movement positioning. The harness should be composed with a soft lining to protect the patient’s skin from the development of sores. Periods throughout the day when the  patient is not wearing equipment should also be provided in case the patient requires a sensory break for the skin to breathe. A variety of ­assistive devices is provided in Table 16.4.

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Company name

Intended use

Ginger Lead Sling™

Abdominal-­thoracic sling Rear-­end support

Four Flags Quick Lift™

Abdominal sling Rear-­end support

RuffWear™

Thoracic support harness

HelpEm Up™

Two-­point lift harness Thoracic and pelvic support

Depending on the surfaces and medical conditions, pets can require extra help in gaining traction to walk. Throw rugs, runners, and yoga mats can help pets move within the house when placed on slick flooring such as tile. Footwear can also be utilized to further help pets gain confidence when walking, but, depending on the animal’s level of strength, footwear can help or hinder ambulation. Using protective footwear for animals with a disability presents challenges in movement. Proprioception through the foot pads is decreased when wearing foot coverings, which may exacerbate a weakness or become cumbersome. Improperly fitted footwear may twist, slip distally, or present challenges to put on. Most have Velcro straps near the opening, rubberized soles to prevent slipping and are machine washable. Customized grip socks are also available and have rubberized tread under the paw surface and may serve the patient better when on surfaces where traction only is desired. In addition to protective footwear, rubberized coatings are available to increase “grip” of the nails. There are numerous examples of pet footwear available (Table 16.5), and it is important to educate owners about wearing times of the various products to avoid secondary interdigital, or dermal infections if left on too long.

16.5.2  Bracing, Splinting, and Prosthesis Orthoses, prostheses, and splinting products are  available for more long-­term protection and/or healing of injuries. Carpal or tarsal

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Table 16.5  Protective footwear and traction aides. Product name

RuffWear™

Dr. Buzby’s Toe Grips™

NeoPaws™

PawFriction Rubber Paw Granules

UltraPaws Dog Boots

Paw-­Paws™

Thera-­Paw Boots

Sticky Pawz

Walkn’ Pets – Walkn’ Boots

OrthoPets® Toe-­Up

Biko Brace Resistance Bands

Rubberized Toe Nail Caps

hyperextension, Achilles tendinopathies, or tears, among other conditions, can benefit from rigid or dynamic stabilization depending on the severity of injury and purpose. Amputees can also benefit from prostheses that can assist in regaining appropriate biomechanics of the pet. K9 Orthotics and Prosthetics (Beaver Bank, NS, Canada), My Pet’s Brace (Morgantown, PA) and Orthopets (Denver, CO) all provide custom-­fit orthotic and prosthetic devices that allow veterinary practitioners to create a cast mold of the patient’s limb based on specific instructions and measurements required by each company. The casting is then sent to the company, which will fabricate a ­custom orthotic or prosthetic to ship back to the veterinarian for fitting to the patient. There is also a company called UPets (Westminster, CO) that provides economical, temporary splints that can be customized in your veterinary office to be worn until a more permanent orthoses arrives. Companies such as Therapaw (Lebanon, NJ) are also capable of creating custom or over the counter braces to assist in cases where a splint or support brace is required in lieu of serial splinting and bandaging for cost effectiveness, ease to ­owners, and patient comfort.

16.5.3  Kinesio Taping Although Kinesio Tape (KT) became popular during the 2008 Olympics, a variation of it has been used since the 1970s when it was first

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developed. Though there are many taping ­techniques in humans, animals have slightly different outcomes due to their haircoat, dermis, subcutis layers, overall anatomy, and behavior. KT has been studied and used most often in the equine species. In humans, there is conflicting evidence on effectiveness. In one equine study with use of a triaxial accelerometric device, the horses where KT was applied increased in longitudinal activity and benefits lasted into the postworkout session (Biau and Burgaud  2022). Another study demonstrated that KT increases epidermal-­dermal distance and with histological evidence, ­taping may reduce edema, inflammation, and pain sensation (Kafa et  al.  2015). Mounting evidence is demonstrating how this therapeutic tool can improve poor joint alignment through sensory input, thus improving proprioception. Utilization of KT techniques may also reduce inflammation by increasing mobility of the dermal layers, decreasing the sensation of pain by activating silent nociceptors and reducing spasms by preventing over contraction of muscles (Gligor and Gligor 2018). A CrVT utilizing KT therapy on animals must have an understanding on where to apply the tape for optimal outcomes. Guidelines for ­successful treatment includes the way KT is cut, placed, and applied with proper patient positioning and appropriate stretch of the tape. Contraindications to KT use include skin disease and infection, open wounds, lesions or malignant tumors, areas of hair loss due to injury, neurogenic components (i.e. nerve root concerns), hotspots, and underlying metabolic or kidney disease.

16.5.4  Environmental Modifications Caring for a disabled pet can be physically and emotionally challenging for caretakers and must be supported as the pet’s needs change over time. Some pets may be disabled for a brief recovery period, while others may remain disabled permanently. The surfaces and physical challenges a patient encounters every day, which may be affecting the quality of life,

16.6  ­Therapeutic Modalities and Emerging Treatment

should be reviewed and modified as needed to improve independence and reduce disability. Patients may need additional support to get on and off bedding, which should be easily stepped into for patients suffering from decreased joint flexibility or challenges in balance. In severely disabled pets, bedding needs enough padding to protect bony prominences from the development of decubitus ulcers and allow for adequate ventilation of the skin for patients susceptible to soiling themselves. On occasion, multiple beds and water bowls throughout the home may be needed to provide alternative sleeping areas for restless or deconditioned patients. Adjustments for feeding strategies may include elevation of food and water bowls (Figure 16.12) (patients with decreased mobility or neurological compromise may prefer eating from plates), assisted feeding when standing, or providing meals while encouraging/assisting the pet to remain in a square sitting or sternal position. Rugs or yoga mats can be placed in slippery areas of the home (around corners) and in the feeding area and baby gates can be used to prevent stair access or limit range access in the home. Ramps or stairs may be needed to improve access to the environment; however, they can be too narrow or steep. In cases where ramps are too difficult, training on flat platforms and gradually increasing the slope angle may be required to improve confidence with equipment, along with using a harness to prevent

Figure 16.12  Dog eating out of an elevated food bowl with traction flooring to prevent slipping. Courtesy of Johanna L. Hagler.

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falls. Steps can be useful to help pets navigate furniture or vehicles, but they may prove difficult for the patient depending on the depth and rise height of the stair. Stairs should also be firm to help the pet maintain stability while going up and down. Finally, some pets require additional quiet retreats so they can rest undisturbed, especially if the household is noisy.

16.6  ­Therapeutic Modalities and Emerging Treatments 16.6.1  Superficial Thermal Therapies Superficial thermal agents are frequently used to treat hospitalized patients and often continue through the time of discharge. Commonly utilized superficial thermal agents include cryotherapy and heat therapy. Both are effective in altering cellular metabolism and providing pain management through the physical laws of heat transfer, conduction, and radiation. Thermotherapy, or heat therapy, is the ­addition of heat via an external device to the body to raise tissue temperatures. Heat therapy alters the neurophysiology order of sensation by elevating the cutaneous thermal receptor pain threshold, and inhibiting pain transmission at the dorsal horn of the spinal cord. With  nociceptive impulses altered, treatment of painful conditions improves the overall patient pain experience. The energy transfer is quickly carried away by local circulation and tissues lose any changes in temperature in a manner of minutes once treatment stops. Tissue depth penetration can reach about 2 cm into tissues with less than a 1 °C (33 °F) change compared with 3 °C (37.4 °F) at 1 cm tissue depths. In general, heat therapy is used for patients experiencing pain secondary to stiffness and/or decreased ROM. After an injury, heat therapy is most appropriately applied after the acute inflammatory phase of tissue healing has resolved and the reparative or remodeling phases of tissue healing have started (e.g. 72 hours and beyond after injury).

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If thermal therapy is applied too early, it causes swelling, pain, and exacerbation of cellular metabolism. Heat therapy is contraindicated in  regions of active bleeding, acute inflammation, cardiac insufficiency, fever, malignancy, decreased or impaired circulation, infection or  known poor thermoregulatory capabilities. Precautionary measures include regular assessment of the original injury or condition, patient level of consciousness, and overall physiologic health. Adverse thermoregulatory events do occur with heat therapy in the anesthetized patient, causing burns or hyperthermia. Patients with extreme obesity or significantly low body mass should be monitored regularly to prevent adverse side effects. Heat can be applied to the affected area with a commercially available heat pack. Treatment times can last about fifteen to thirty (15–30) minutes or longer depending on the severity of muscle soreness. Cryotherapy is the addition of an external cooling device to the body to decrease tissue temperatures up to two (2) to four (4) centimeters with superficial applications. The neurologic response to cryotherapy is mediated by peripheral thermal receptors and is categorized based on myelination, size, and nerve conduction velocity. Cryotherapy can help reduce pain by causing vasoconstriction, which can help decrease pressure on nociceptors and can decrease hemorrhage, control spasms, and reduce pain and edema after exercise. To avoid burns, the pet’s skin should be checked regularly for mottling, blanching, or other discolorations. Cold is commonly used for acute injury or after surgery in the first forty-­eight to seventy-­two (48–72) hours. There are many versions of commercially available cold packs that are convenient and that retain cold temperatures for long periods of time but are not as effective as ice. The easiest method is crushed ice placed in a double-­wrapped plastic zipper-­top bag filled with two parts water and one part rubbing alcohol and frozen overnight. A thin dry cloth should always be between the cold pack and the patient’s skin to reduce infection and injury to the skin. Ice cups are

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ideal for small joints and applying a mild amount of localized compression. They can be made by filling a paper cup with water and a wooden stick placed inside. Once the water is frozen, the paper is peeled away and the wooden handle can be used to apply the formed ice to the desired joint. Other forms of cryotherapy include veterinary cold compression systems, cold immersion baths, ice towels, vapocoolant sprays, and contrast baths. Cryotherapy can be applied to nearly any region of the body; however, precaution should be used in superficial regions around peripheral nerves (e.g. peroneal and ulnar nerves) because they have been known to cause cases of cold-­induced nerve palsy in humans. Patients with generalized or localized vascular compromise or who possess an impaired ability to thermoregulate should receive cryotherapy conservatively. Patients with regions of poor sensitization, the very young, and very old may receive cryotherapy but with precaution. Extreme precaution should be taken in the anesthetized or sedated patient because of their inability to communicate adverse effects. Contraindications to cryotherapy include cases of known nerve damage, open wounds forty-­ eight (48) to seventy-­two (72) hours after injury, and a history of cold urticaria causing wheals and swelling on the skin from histamine release. Duration of cryotherapy treatments in animals varies depending on location, patient body size and compliance. Recommendations for dogs have been extrapolated from human rehabilitation and for most cases, are applied during the first 24–72 hours following acute injury when the acute signs of inflammation are present (swelling, redness, heat, and pain). Cold packs can be applied for 10–20 minutes, depending on the muscle location and patient size up to every 3–4 hours in the postoperative patient. Small-­breed dogs and cats should not exceed 10 minutes of cryotherapy for the proximal extremities and 15–20 minutes for vertebral injuries. Medium-­to large-­breed dogs with a larger surface area and muscle mass compared to smaller animals may receive up to

16.6  ­Therapeutic Modalities and Emerging Treatment

20 minutes of treatment at proximal extremities and vertebral column and 10–15 minutes to  the distal extremities (elbow, tarsus, digits, metacarpals, and metatarsals).

16.6.2  Photobiomodulation (Therapeutic Laser) Therapeutic LASER, an acronym for Light Amplified by Stimulated Emission of Radia­ tion, alters cellular function by modulating a process known as photobiostimulation. Photo­ biomodulation (Anders et  al.  2015) can be used for a variety of acute and chronic pain conditions and is defined as a nonthermal interaction of monochromatic radiation within a target site, stimulating cellular mechanisms like mitochondrial respiration and ATP synthesis to accelerate healing or regeneration. The most common application of therapeutic laser is as an adjunctive therapy in the ­management of chronic pain conditions like osteoarthritis, but it may also be used for ­musculoskeletal, tendon, or ligament injury, reduction of scar tissue formation, treatment  of myofascial trigger points (MTrPs), stimulation or sedation of acupuncture points, improvement of chronic or acute skin wound healing times, reduction of localized bacterial counts, improved vascular and lymphatic flow, stimulation of nerve regeneration, and pain management (increasing the release of endorphins and enkephalins). All lasers emit tiny packets of energy, called photons, from an emitter aperture and are absorbed by chromophores on cytochrome c within mitochondria and in cell membranes. Different types of lasers are available for medical or therapeutic use and differ in maximum power output. Therapeutic lasers are classified by the Food and Drug Enforcement Agency (FDA) on their level of safety and ability to cause injury to tissues, especially the eye, through thermal damage. Four safety classes are recognized by the FDA, which are determined by power output (in watts) and wavelength. The most common therapeutic lasers

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used are 3B (500 mW to 30 mW) and 4 (1–15 W). Laser power is measured in a unit of time expressed in watts (W) or milliwatts (mW). Power determines the dose or energy density and is measured by the number of joules (J) delivered per surface area, measured in cm2 (1 W = 1 J/s), to tissues. Calculation of time is required for treatment delivery and can only be determined if output power of the laser and desired total dose for the condition are known. Lasers with higher output powers will be able to deliver treatment dose faster and do not affect absorption depths. For example, to provide 1 J of energy density from a 500 mW laser, the probe aperture would need to be held in one spot for two seconds to deliver 1 J of energy density (e.g. 1 J = 1 W/s; 500 mW = 0.5 W; 1 W/ 0.5 W  =  2 seconds). Protocols are listed in Appendix 16.D. Therapeutic laser wavelength falls between the infrared or near infrared portion of the electromagnetic spectrum at 600–1200 nm, with most therapeutic lasers producing wavelengths between 820 and 904 nm. Wavelengths in the near infrared ranges penetrate tissues the deepest of all waves in the visible spectrum, making treatment of deep tissues, trigger points, ligaments, joint capsules, and intra-­articular structures possible while longer wavelengths closer to the visible spectrum stimulate superficial tissues and are best suited for acupuncture point stimulation or wound healing. Laser energy can penetrate tissues directly up to 2 cm and indirectly up to 5 cm (so the joint capsule of a large dog will not be directly affected) however thick hair coats may affect absorption depths. Depending on the therapeutic laser power output, patients with dark skin or fur may need the laser aperture moved more frequently or have fur shaved to reduce the melanin in pigmented areas absorbing laser light faster, causing heating effects. Retinal damage can occur to the therapist or patient if the beam is directed or reflected into the eye. Protective eyewear rated to be used with the laser wavelength of the laser being used is recommended for the person delivering

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treatment. Currently, several companies make a commercial brand of sunglasses for dogs in the form of tinted goggles designed to fit the shape of a dog’s head for protection during laser therapy. However, the safety rating of the glass blocking the wavelength used must be verified. An alternative safety precaution in cases where goggles cannot be used on the patient includes using an opaque Elizabethan collar or visual blockade such as a towel in front of the patient’s eyes. Therapeutic laser use is contraindicated over a pregnant uterus, open fontanels, tattoos, growth plates of skeletally immature animals, the gonads, malignant areas, and directly into  the cornea and in areas of hemorrhage. Precaution is taken in photosensitive areas of the skin, recently traumatized or injured tissues with mechanical hypersensitivity, and areas treated with medications or solutions. Patients receiving laser postoperatively must have any remaining iodine or povidone removed from the skin to avoid laser light absorption by the aseptic solutions being intensified and becoming painful. Topical medications, especially ­corticosteroids or transdermal opioids, may produce negative systemic effects and should be removed from treatment areas several hours in advance to avoid complications.

16.6.3  Electrical Stimulation Electrical stimulation (ES) is a therapeutic tool using electrical current to treat orthopedic, neurological, and muscular disorders and (a)

in 1990, a committee of the electrophysiologic section of the American Physical Therapy Association (APTA) developed the Standards of Electrotherapeutic Terminology, a document created to unify and standardize the terms and definitions. Depending on the type of electrical stimulation utilized, biological effects will differ. Electrical muscular stimulation (EMS) stimulates a denervated muscle directly by its  muscle fibers. Transcutaneous electrical nerve stimulation (TENS), shown in Figure 16.13, is an electrical modality used in pain management and is a low-­frequency form of neuromuscular electrical stimulation (NMES), which stimulates a target muscle or  tissue via an intact nerve. Pain is being ­controlled through the gate control theory, endogenous opiate release, and the counter-­ irritant theory (Melzack and Wall  1965) with  either high-­frequency, low-­intensity (acute pain) or high-­intensity, low frequencies (chronic pain). The goal of TENS in pain management is  to  activate inhibitory neurons to block pain transmission from the dorsal horn. Endogenous opiates include shorter acting enkephalins (released with high-­frequency, low-­pulse duration stimulation) and longer-­ acting endorphins (low-­frequency, high-­pulse duration stimulation). TENS used for acute pain is effective during a treatment but has little residual effect. Appendix  16.E: Electrical Stimulation provides example protocols. Many units are cost-­effective and easy to use, and they may be suitable for owner use at (b)

Figure 16.13  (a) TENS Electrode pad placement for caudal lumbar paraspinal pain (b) NMES Electrode pad placement for muscular stimulation of the caudal thigh and hip musculatures. Courtesy of Johanna L. Hagler.

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16.6  ­Therapeutic Modalities and Emerging Treatment

home. TENS uses rubber electrode pads placed on the skin to deliver an electrical current. Fur can hinder good pad contact; therefore, the fur beneath where the pads are being placed may need to be shaved. In dogs and cats that have easily parted fur, good contact may be achieved by using electrode gel. For pain control, the  electrodes can be placed on either side of  the pain site (e.g. the medial and lateral aspect of a joint) or over muscle motor points. Contraindications to using TENS include patients with seizure disorders, pacemakers, or directly over an area of thrombosis or neoplasia. The parameters that are controlled by the  operator include pulse duration (μs), ­frequency (Hz), amplitude, ramp time, and length of treatment.

increasing the pain threshold as well as inhibiting neurotransmitters, such as Substance P, which contribute to pain. The exact mechanisms behind the pain-­relieving function of ESWT are not well known but are thought to increase serotonin activity in the dorsal horn and descending, inhibiting pain signals. Contraindications and precautions for ESWT include over implants, excessive energy levels over smaller regions (tendons and ligaments), acute inflammation, immune mediated disease, neoplasia, open-­growth plates, infection, unstable fractures, neurological deficits, coagulopathies, and delivery over body cavities – including the lungs, heart, eye, major organs, blood ­vessels, and a gravid uterus (Mucha and Millis 2019).

16.6.4  Extracorporeal Shock Wave Therapy (ESWT)

16.6.5  Therapeutic Ultrasound (ThUS)

Shockwave therapy uses acoustic sound waves to affect cellular and biological processes. Sound waves can be radial or focused depending on how they travel through tissues and focused shockwaves are delivered through ­piezoelectric, electrohydraulic, or electromagnetic methods. Specialized handpieces (or trodes) deliver energy by making contact with the treatment area using coupling gel. High-­ energy, high-­amplitude acoustic pressure waves behave like sound waves in tissue, and as the waves travel through soft tissue and fluid, energy is released into the tissues when a change in density is encountered, such as at the interface between bone and ligament (Millis et al. 2004). Shockwave treatment can reduce inflammation, provide short-­term pain relief, improve blood flow, increase bone formation, realign tendon fibers, enhance wound healing, and provide pain relief. This treatment modality typically requires sedation due to the sound and pain elicited, although there are newer ESWT units on the market that may not require sedation. Acoustic soundwaves applied to an area of chronic inflammation may promote analgesia by acute hyperstimulation of nociceptors and

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ThUS, is used for tissue heating using a transducer with a piezoelectric crystal to produce high-­frequency acoustic waves that travel through tissues to increase collagen extensi­ bility, blood flow, pain threshold, macrophage activity, nerve conduction velocity, alter enzyme activity, and decrease muscle spasm. As soundwaves move through tissues, molecules are compressed and decompressed, causing biological effects. Tissues can be warmed 1–4 °C (33–39.2 °F) for thermal effects and ­useful in tendonitis, joint contracture, wound healing, bone healing, and muscle spasm. Frequency determines the depth of tissue ­penetration, and commonly used parameters include 1.0 Megahertz (MHz) and 3.3 MHz. One (1) MHz is absorbed at a depth of 2–5 cm, while 3.3 MHz penetrates to 0–3 cm. Treatment modality can be by pulsed wave (PW) or continuous wave (CW) ultrasound. PW US allows for higher intensities, delivered in bursts for a specific time period and can be used without damaging the tissues. It is commonly used for acute conditions to promote wound healing and to treat inflammatory diseases of joints and tendons. CW US delivers waves continuously, which inherently raises the risk of tissue injury and is used predominantly for chronic

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conditions. The mode (continuous or pulsed) and intensity are chosen during treatment and affect the amount of energy delivered. As an example, when pulsed at a 1 : 4 ratio, the average amount of energy delivered is 0.5 W/cm2 (in continuous mode only 0.1 W/cm2 is needed to heat tissues to the same extent). When performing a ThUS treatment, coupling gel must be used to minimize air reflecting most of the ultrasound waves, therefore clipping the fur increases treatment effectiveness. The US transducer is held perpendicular to the skin and constantly moved over the treatment area to prevent burns. Contraindications to therapeutic US include acute inflammation, over tumors, on sites of infection, over sites of decreased sensation, directly over the eyes, heart, or pregnant uterus, and over epiphyseal plates that are not closed (Armitage and Millis 2019).

Figure 16.14  Patient receiving tPEMF to the shoulder. The treatment field is within the inner circle of the ring. Courtesy of Johanna L. Hagler.

16.6.6  Electro-­Magnetic Therapy

16.7.1  Myofascial Trigger Points

Electromagnetic field therapy (EMF) can be produced by static (permanent) or pulsed radiofrequency fields. EMF therapy is influenced by multiple factors, including the interaction of matter with a magnetic field, called magnetic susceptibility, and distance from the EMF. Pulsed EMF (PEMF) has gained ­popularity in the rehabilitation field and relies on low-­frequency PEMF, with varied characteristics in wave types and amplitudes depending on the manufacturer. It is proposed that PEMF therapy provides analgesic and anti-­ nociceptive effects like opioids, although a definitive ­biologic or biochemical mechanism of action remains unclear and supporting ­veterinary studies are sparce (Prato et al. 1995). PEMF accelerates the  removal of inflammatory ­mediators, which, in turn, resolves pain  (Pilla et al.  2011; Bredt  2003). In one FDA  approved ­non-pharmaceutical ­anti­inflammatory device  – targeted PEMF (Figure 16.14), the technology specifically targets the nitric oxide ­signaling  pathway that accelerates the anti-­inflammatory cascade. PEMF BioPulse mats, blankets, and loop

A manual therapy, myofascial trigger point is defined as a “hyperirritable spot located within a taut band in skeletal muscle” (Travell and Simons 1983; Wall 2014). Identification begins with observation of posture, movement, and client history and is confirmed with the ability to skillfully palpate and detect these regions of muscle ­tissue abnormalities (Appendix  16.F and Appendix  16.G). MTrPs have autonomic, sensory, and nerve components (Wall  2014). They can form after injury or from overuse or overloading muscles in which low-­level muscle contractions can lead to decreased perfusion, ischemia, and hypoxia as a cellular response to activation of chemical substances affecting neuropeptides (Wall 2014; Conarton 2019). MTrPs and myofascial pain syndrome (MPS) have been demonstrated as both causation and because of acute and chronic pain in veterinary patients. Trigger points (TP) and myofascial pain were first coined by Dr.’s Janet Travell and Seymore Rinzler in the 1950s. A manual on MTrPs was published by Simmons and Travell in the 1980s and since this time, research in both human and veterinary

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systems are commonly used to deliver ­treatment both in veterinary rehabilitation practices as well as in the home setting.

16.7  ­Manual Therapy and Myofascial Trigger Points

16.7 ­Manual Therapy and Myofascial Trigger Point

medicine has made a positive impact on the treatment of these conditions (Travell and Simons  1983). Recently, the work of Jan Dommerholt DPT and Dr. Rick Wall DVM to support veterinary practitioners has been instrumental in elevating the care and role the CrVT plays in the identification and treatment for MTrPs and MPS. This additional training not only facilitates client education but also provides hospital staff with a tool as they treat their veterinary patients. Treatment includes both invasive and noninvasive techniques (Appendix  16.H) that can improve existing conditions and support veterinary patients in returning to normal or closer to normal function. A  2006 review by Simons and Dommerholt presented an analysis of studies, including the endocannabinoid system and its role in fascial reorganization and reduction of inflammation in myofascial tissues; positive effects of MTrP injections with botulism type A; and central representation of hyperalgesia from MTrPs  – all of which may spur future studies on this important topic in veterinary pain management. Professional training in MTrP therapy includes understanding diagnostic methods, which may include a clinical approach and support of diagnostic measurements (i.e. ultrasound, EMG, etc.) and ability to perform ­invasive and noninvasive treatments (Sato et  al.  2020). A CrVT educated in MTrP and MPS benefits their patients, the rehabilitation team, and the clinic through an integrative approach to improve outcomes and enhance existing pain management protocols and programs in veterinary medicine.

16.7.2  Joint Mobilizations and Chiropractic Joint mobilizations (JM) are passive manual therapy techniques that can be used to improve joint ROM and provide pain relief for arthrokinematic restrictions. They can be considered oscillatory or as a sustained stretch and are achieved by gliding one joint surface on an

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opposed stabilized joint surface. JM are dependent on the range of the mobilization applied and also at which point in the range the mobilization is applied. Oscillatory joint mobilizations should be applied on joints that are restricted in movement, whereas sustained mobilization should be used for restrictions of the muscle, tendon, or skin. In cases requiring tissue elongation, a low-­intensity, repetitive stretch should be used. In cases of tissue ­contraction, sustained stretching should be used. Five (5) grades of mobilizations are utilized for therapeutic purposes, depending on the cause of pain or restriction in joint motion (Appendix  16.I). Selecting the correct joint mobilization grade and direction of gliding to use are important to avoid causing additional pain. If the ROM is decreased due to pain, typically Grade 1 or II mobilizations should be used in a range that does not cause pain to the patient for 30 seconds or more. If the ROM is decreased due to joint stiffness, Grade III or IV mobilizations are utilized and generally are performed toward the stiffness for one (1) minute or longer. After each mobilization, joint ROM is evaluated to determine whether additional treatment is needed (Gillete and Dale 2014). Grade five (5) joint mobilizations, depending on the practitioner’s philosophy and training, are musculoskeletal manipulations, better known as chiropractic manipulation. Humans routinely seek out chiropractic care for a number of reasons, most often due to back pain. Chiropractic care for veterinary patients has become more common. Veterinarians and chiropractors trained in veterinary chiropractic are the only practitioners who may perform manipulations on animals; however, the CrVT plays an important role despite the inability to perform a “grade V” mobilization. Trained CrVT’s may be utilized to provide stability to the area of focus to enable the veterinary practitioner to isolate the spinal segment for adjustment to ensure the force reaches the intended tissue. The Grade V mobilization involves a specific short-­lever and high velocity-­controlled force

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that differentiates it from other types of mobilization and is done by pushing the facet joint surface to the anatomical limit of joint play. The intention of joint manipulation is to restore motion and proper bony relationships, reset neural receptors back to healthy firing frequency, assist with neurologic healing, rebalance muscle tone and function, and reduce pain (Jurek 2013).

16.7.3  Joint Range of Motion – Passive PROM therapy is useful in diminishing the effects of disuse, immobilization and preventing contracture. This manual therapy should be used whenever a patient is unable to move the joint, active motion is contraindicated after  surgical procedures, in the treatment of  chronic musculoskeletal disease, and in patients lacking the strength or nervous system health to produce a normal gait and to maintain integrity of the tendon, ligament, articular cartilage, and muscle. The motion of a joint is performed without muscle contraction and remains within the patient’s available ROM, using an external force-­ the hands of a therapist-­ to move the joint in a neutral plane of movement. PROM therapy can maintain normal ROM by periodically moving joints and muscles throughout their available ranges but cannot prevent muscle atrophy, increase strength or endurance, or assist with circulation to the extent that voluntary muscle contraction does. PROM therapy is contraindicated when motion may result in further injury or instability, such as with unstable fractures near joints and unstable ligament or tendon injuries. Precaution should be taken in patients with acute or chronic inflammation because local edema and joint effusion may mechanically limit joint motion or cause pain with increases in joint capsule pressure. Technique involves gently extending and flexing individual joints through a comfortable ROM to not injure joint structures. The patient should remain pain-­free during the therapy time and not react negatively to any movements.

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Overaggressive PROM exercise will result in pain and delayed use of the limb. For most routine conditions, each joint should go through 15–20 repetitions and be performed 2–4 times a day, spaced evenly apart. As ROM returns to normal and tissues regain normal plasticity, the frequency can be decreased, and active ROM exercise therapy replaces manual ­therapy exercise. Appendix  16.J details hand positioning and joint movements.

16.7.4  Therapeutic Massage Massage provides positive influences on the physical and psychological well-­being of all ages and conditions (Hourdebaigt 2004) and is the most effective means of relaxing a stressed animal (Dunning et  al.  2005). It serves as a ­prevention measure against injury in the management of competitive athletes, aides with pain relief, improves mobility in disabled or compromised patients, and can produce immediate effects to improve healing, initiate nervous system sedation, reduce tension, and strengthen the bond between the patient and owner at home (Sutton  2004). Effects from therapeutic massage include mechanical or reflexive responses. Mechanical effects occur from actual physical contact caused by pressure applied on the body and its tissues. The degree of mechanical effect is directly pro­ portional to the amount of pressure applied to tissues (Hourdebaigt  2004) and the direction of  massage strokes. Mechanical effects include  the following: lymphatic and venous drainage, removal of edema and metabolic waste, increased arterial circulation (Dunning et  al.  2005), breakdown of adhesions, muscle  relaxation, increased mobility, and a ­reduction in stress hormones, which may lead to lower  blood pressure, slowed breathing, improved digestion, and release of endorphins. Lymphatic flow improvement is caused by increased capillary, plasma osmotic and interstitial fluid pressure, and capillary permeability. Massage is also believed to replenish fluid in tissue spaces, producing a flushing effect

16.8 ­Emerging Therapeutic Medical Intervention

Table 16.6  Therapeutic massage indications. ●●

Reduction or prevention of venous stasis and lymphostasis

●●

Mobilization of adhesions

●●

Regulation of muscle tone

●●

Preparation of muscles for physical training, preventing injury

●●

Acceleration of muscle recovery after training

●●

Decrease fatigue and soreness after training

●●

Maintain flexibility and prevent further loss of function, decrease edema/inflammation after surgery

●●

Chronic musculoskeletal problems (such as OA), which develop into postural and gait compensations from muscle tension

●●

Improving joint and muscle function

●●

Preservation of the owner and animal bond

Table 16.7  Precautions and contraindications for massage therapy. ●●

Open wounds

●●

Unstable fractures

●●

Severe pain

●●

Coagulation disorders

●●

Certain types of neoplasia

●●

Shock

●●

Fever

●●

Acute inflammation

●●

Skin problems

●●

Infectious disease, or acute stages of viral disease

and bringing in additional nutrients. From human literature, chemical irritants in the tissues such as Substance P, prostaglandins, and waste products of metabolism, decrease pain thresholds by sensitizing free nerve endings. By replenishing tissue fluids, inflammatory products are removed, sensitization is reduced, and some types of chronic pain are prevented or reduced. Tables 16.6 and 16.7 provide additional details for massage therapy. During a massage therapy session, the therapist must be relaxed and utilize ideal body mechanics or ergonomic tools to reduce strain on the body. The environment should be calm and free of distractions, and the patient should be relaxed on comfortable bedding. Movements

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of the therapist’s hands should be slow and organized, following a sequence or pattern from superficial to deeper strokes returning to lighter strokes in the end. The pet should be monitored for signs of pain and the length of  the session is guided by the pet tolerance but should ideally last at least twenty (20) minutes. When performed by a therapist, medical notes are to be documented in a record and should include the following: areas of heat, tissue restrictions, the pet moving away or changing position, and duration of treatment. Appendix  16.K summarizes common therapeutic techniques for management of pain and wellbeing. Pet owners can be taught to perform massage therapy on their pets at home utilizing the stroking and effleurage techniques, along with education regarding behavioral recognition for signs of pain during a session.

16.8  ­Emerging Therapeutic Medical Interventions 16.8.1  Regenerative Medicine and Biological Treatments Biological therapies, or regenerative medicine, is using the body’s own reparative mechanisms to repair tissues and alleviate pain and inflammation. It has become more available with the

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advent of point of care technology and accessibility of equipment that specializes in providing stem cells or platelet rich plasma (PRP) products for veterinary patients to augment surgical intervention and slow down or arrest some degenerative processes with long-­term effects. Regenerative medicine encompasses mesenchymal stem cells (MSC) and PRP and can be used to treat conditions such as tendon or ligament injuries, muscle injury, chronic OA, fracture healing, and increasingly neurological conditions.

16.8.2  Corticosteroids and Hyaluronic Acid Glucocorticoids are steroid hormones that maintain cell homeostasis through signaling pathways that change with the needs of the body (Savvidou et al. 2019). Synthetic corticosteroids are beneficial in controlling pain and inflammation associated with osteoarthritis. When a corticosteroid is directly injected into an affected joint, pain and inflammation can decrease significantly, with pain relief lasting up to 4 weeks. The benefits of injecting a corticosteroid into a joint is that a relatively small volume can be used to avoid stretching the joint capsule with a larger volume, it can be a same day appointment for the patient, and it is inexpensive. The side effects associated with corticosteroids can also be avoided since the steroid stays within the joint rather than being systemically absorbed. Triamcinolone acetonide (TA) is most commonly used for joint injections at a dose of 2–5 mg/joint (total TA injected not to exceed 0.5–0.7 mg/kg) (Gamble et al. 2020). Hyaluronic acid (HA) can be used as a joint injection that can alleviate pain and inflammation caused by osteoarthritis. HA is a viscous solution that serves as a chondroprotectant and shock absorber that mimics the role of synovial fluid. In osteoarthritis, synovial fluid loses its viscosity and no longer provides lubrication within the joint. HA can provide the same protection as well as downregulate inflammatory mediators. HA is slightly more expensive than corticosteroids but can also be

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administered same day under sedation. HA can be used in mild to severe cases of OA at a dose of 10–20 mg/joint (Alves et al. 2020).

16.8.3  Stem Cells Stem cells are undifferentiated cells capable of transforming into numerous types of cells in the  body. The most common and easiest to obtain in veterinary medicine are MSCs, which have immunomodulatory and tissue repair mechanisms (Voga et  al.  2020) and are used prominently in orthopedic/arthritic patients. MSCs are usually harvested from fat (falciform or subcutaneous) obtained from the patient under general anesthesia or sedation and a local block and prepared either in hospital or sent to a processing center for extraction of MSCs. This process will likely require the patient to come back for another appointment once the stem cells are ready to be injected after processing. MSCs have numerous growth factors and inflammatory mediators that assist in repairing tendon/ ligament injuries as well as improving comfort and ROM with OA. The stem cells are typically injected either into the damaged tendon/­ ligament or into affected joints under sedation.

16.8.4  Platelet Rich Plasma (PRP) PRP is also commonly used in orthopedic conditions for healing and pain management. Typically, the patient’s own blood is drawn and spun in a centrifuge to isolate a significantly increased concentration of platelets in a small volume of plasma. Platelets contain numerous growth factors, inflammatory mediators, and healing factors to decrease pain in osteoarthritis. Numerous point-­of-­care kits can be utilized in the veterinary clinic that can allow for same-­ day treatment of the patient.

16.8.5  Interleukin-­1 Receptor Antagonist Protein (IRAP) Also known as auto conditioned serum (ACS),  IRAP is an anti-­i nflammatory protein derived  from the patient’s blood to

16.8 ­Emerging Therapeutic Medical Intervention

counteract the effects of the proinflammatory protein Interleukin-­1 (IL-­1). Collection methods are similar to that of PRP, and depending on the collection system, can produce varying levels of IRAP. Currently, no in vivo studies show improvement in canine patients with OA treated with IRAP; therefore, use should be reserved for early intervention strategies. Equine patients with OA treated with IRAP have shown promising clinical results, but no in  vivo studies link composition with therapeutic effect (Armitage and Millis 2019).

16.8.6  Prolotherapy Prolotherapy is a less common regenerative medicine treatment used in veterinary medicine. The theory behind prolotherapy is that by injecting an irritant into a diseased joint you can produce an inflammatory response and an increase in tissue proliferation (Sherwood et al. 2017). The most common substance used for prolotherapy is dextrose, which has been shown in humans to induce localized tissue trauma that results from an osmotic shock that can cause inflammation. In the inflammatory phase of healing increased growth factors, increased prostaglandins and increased cell proliferation occur, all while reducing inflammatory interleukins.

16.8.7  Emerging Technologies: Radiosynoviorthesis (Conversion Electron Therapy) Conversion electron therapy is a recent development in the treatment of elbow pain from osteoarthritis. This product, Synovetin OA® (Exubrion Therapeutics), is an FDA-­approved novel radioisotope (Tin-­117 m) that targets inflamed synovium. In elbow synovitis, the synovium begins to degenerate and destroy articular cartilage, therefore leading to ­bone-­on-­bone contact, causing pain. This radioisotope reduces synovial hypertrophy by  targeting and destroying inflamed cells (Fox and Donecker 2019). This is a long-­acting

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(up to 1 year) single-­joint injection that can be done within the clinic (Aulakh et  al.  2021). This is not considered a drug but a veterinary device. There are no reported side effects, and dogs are free to resume normal activity after ­injection. This can be performed as a same-­day pro­cedure under sedation. It is one of the more expensive regenerative medicine options. There are further studies being ­conducted with hip dysplasia to hopefully also be an approved modality in end-­stage degenerative joint ­disease. Since this is a radioisotope, special training and care of the product must be adhered to in order to avoid any issues.

16.8.8  Emerging Technologies: Viscoelastic Therapies – Injectable Hydrogel Microparticles and Polyacrylamide Gels Intra-­articular injection of hydrogel microparticles can help with osteoarthritis associated pain due to the loss of cartilage or alteration of joint tissue function by improving and supporting joint health. Spryng™ (PetVivo, Inc.) is a patented medical device for use in treating arthritis, joint damage due to ligament and tendon injury, and damaged or lost cartilage. The inert hydrogel-­particles are insoluble and slowly absorb into the surrounding tissues and within the joint. Through the injection, the material acts as a cushion that, over time, integrates into the synovial fluid (and surrounding space) by creating a strong, sterile hydrated biomaterial to mimic natural cartilage. With increased cushioning, the overall mechanical load on joint surfaces during movement is decreased. Spryng is composed of a two naturally derived protein (collagen, elastin) and one carbohydrate. Viscoelastic cross-­linked polyacrylamide hydrogels (PAHG) with silver ions (either 4% or 2.5%) were originally developed as a joint treatment and augmentation of connective tissues in humans, respectively (Tnibar et al. 2017). The weighted PAHGs have different target tissues and mechanism of action. The 4% PAHG targets cartilage and is

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proposed to coat the cartilage with a protective lubricating layer to reduce friction in the joint between two opposing surfaces (Vishwanath et  al.  2023). The 2.5% targets the synovium, increases synovial cellular integration and proliferation and increases joint capsule elasticity (Christensen et al. 2016)

16.9  ­Therapeutic Exercise and Aquatic Therapy 16.9.1  Therapeutic Exercise Principles and Application Access to specialized equipment does make rehabilitation more effective; however, adequate care can be achieved without investing a  significant amount of space, requiring ­specially trained personnel to deliver treatments, or significant financial investment from the practice. The most commonly ­prescribed form of physical rehabilitation is therapeutic ­exercise and is considered an essential com­ponent for successful postoperative ­outcomes and management of chronic conditions. Indications may include musculoskeletal ­disorders, nervous system disorders, inflammatory or metabolic musculoskeletal disorders, congenital or acquired musculoskeletal disorders and associated deformities, muscular imbalance and dysfunction, disuse after ­immobilization, and loss of limb due to an amputation (Wittek and Bockstahler  2019). Precautionary measures should be taken in those animals with debilitating cardiac disease, tumors that impact mobility, and behavioral dysfunction affecting interaction during therapy. Absolute contraindications include acute disorders affecting the cardiovascular system, acute venous thrombosis, acute neurological disorders causing compression and sensory loss, acute musculoskeletal disorders such as fractures or soft tissue disruptions, acute inflammatory disease that is accompanied by fever, and any condition that deteriorates with exercise.

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Therapeutic exercise has varying effects on the body and is designed to improve recovery rates, strength, endurance, enhance pro­ prioception and neuromuscular awareness; ­facilitate balance; and prepare the patient for more active exercise (Bockstahler et al. 2004). Typically, some form of manual therapy (joint ROM, stretching or massage) is included, along with aerobic conditioning, muscle strengthening, endurance training, and correction of gait abnormalities. Animals with bilateral pelvic injuries, neurological injury, age-­related weakness, and severe deconditioning benefit the most from a ­therapeutic plan. Assisted-­standing exercise may be more appropriate in early stages of recovery or strengthening, utilizing devices such as body slings or mobility carts. Proprioceptive exercises help regain the ability to ­appropriately use and place limbs and can include weight-­shifting, balance boards (Figure 16.15), and air-­inflated exercise balls or peanut-­shaped rolls. Patients with enough strength and mobility may perform an active ROM exercise such as cavaletti pole walking to encourage momentary weight bearing on affected limbs, increased joint motion,

Figure 16.15  Balance boards help with proprioception and balance. Therapists must provide stabilization to equipment through assistive devices or physical stabilization depending on patient strength. Different muscle groups are targeted depending on the direction of board excursion and patients can benefit from this exercise in standing, sitting, or lying down positions.

16.9  ­Therapeutic Exercise and Aquatic Therap

Figure 16.16  Walking (or trotting) over cavaletti rails results in a significant increase in flexion of various joints. The height of the cavaletti rail can be raised and lowered depending on the desired therapeutic outcome. Courtesy of Johanna L. Hagler.

proprioceptive awareness, and balance (Figure 16.16). Plans are developed individually for each patient to address functional limitations and may focus on early limb use or strengthening, speed, or endurance using baseline values of joint motion, muscle strength, balancing ability, and disability or postural tendencies. Activities can be performed in the clinical setting or at home. Details, including variable parameters in frequency of work, speed or intensity, duration, and environment conditions are described in the plan. Generally, in the first two 2–3 weeks of rehabilitation, daily to twice daily exercise is recommended to avoid overuse injury. As therapy progresses, activities are modified by increasing the frequency and intensity to prevent muscular adaptation and stagnation of conditioning. In all stages of therapy, adequate rest periods between sessions should be included to prevent compensation or poor-­quality execution, depending on the condition and phase of rehabilitation. For severely deconditioned, neurological, or senior patients, principles of low-­duration, high-­frequency exercise intensity are followed. In cases where rest for 2–3  days does not improve exercise quality, patient treatment should cease and pain ­during therapy must be considered. Patients progressing normally through an exercise

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program may have the duration of activities increased 10–15% each week until goals are met. The types of exercise available for therapeutic purposes are extensive, and on occasion specialized equipment can be helpful to improve the quality of execution. Appendix 16.L details commonly utilized exercises and their intended purpose. Whenever possible, patients should attempt to complete the activity independently; however, assisted therapeutic exercises using multiple handlers and assistive devices are useful for patients with mild to moderate deficiencies in the ability to stand or ambulate well on their own. During these exercises, the therapist can position patients and may maintain ­constant contact to ensure the proper stance for the exercise is maintained. Assisted exercise ­sessions typically are of short duration because de-­conditioning is severe, and fatigue occurs rapidly. As patients improve, the amount of assistance can be decreased and the duration of exercise increases. Appendix 16.M highlights sample guidelines for specific conditions.

16.9.2  Land Treadmills Land treadmills can improve gait patterning, limb use and build muscles symmetrically in addition to controlled leash walking. Stress and pain of limb movement can be reduced by aiding in extending the hip and stifle through the stance phase of gait and helps to build muscle by encouraging symmetrical use of limbs while walking. Patients without physical disability should wear a nonrestrictive harness to prevent falls and maintain control during activity. Other patients may need more support from a harness encompassing the thoracic or pelvic limbs (or both) to accommodate disability. Severely disabled patients may require a therapy stand spanning the treadmill belt to assist the therapist with therapeutic gait patterning. Many human treadmills are suitable for canine patients, but depending on the breed, achieving a full stride can be affected

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Table 16.8  Benefits of aquatic therapy. Decrease pain during movement

Muscle relaxation

Enhance coordination and balance

Manage obesity

Palliative support (oncology)

Increase metabolism

Strengthen muscles

Encourage limb use

Decrease weight bearing

Reduce edema in distal extremities

Strengthen core musculatures

Increase superficial circulation

Increase metabolism

Improve muscle tone

Enhance fitness

by belt length. Small dogs can generally get by with using a 4-­ to 5-­foot-­long belt, but large dogs require a minimum of 6 feet to achieve proper limb extension. Additionally, side walls or physical barriers can prevent patients from stepping off the treadmill itself, which may cause injury. Ideally, treadmills include features such as incline or decline, quick-­release emergency stop triggers, and even reversal of belt direction. Belt speed should be slow enough for the therapist to perform gait patterning or accommodate even the smallest patient (approximately 0.4 mi/h 0.64 km/h), and the belt should start with the push of a button instead of the patient walking to initiate or control belt movement.

16.9.3  Hydrotherapy or Aquatic Therapy Aquatic therapy can provide patients with early weight bearing postoperatively, assist with standing, improve conditioning and endurance, improve strength, increase joint ROM, reduce pain, and provide psychological benefits (Levine et al. 2004). Aquatic therapy offers movement that is functional, mechanically correct, and muscularly challenging while decreasing pain levels. Buoyancy aids in the rehabilitation of weak muscles and painful joints, allowing patients to exercise with minimal weight bearing on joints (Miller  2000) and encompasses any exercise or manual therapy performed in an aquatic

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environment for a variety of conditions and therapeutic goals (Table  16.8). Therapeutic benefits from aquatic therapy differ from land-­based exercise and are derived from the physical properties of water, including buoyancy and density, viscosity, resistance and surface tension, hydrostatic pressures, and thermal benefits. Muscle relaxation and increased metabolism occur in warm water, helping exercise to occur without needing a period of warming up (compared to land-­based therapy). Water temperature should be maintained between 82 °F (27.7 °C) and 86 °F (30 °C) (Nganvongpanit et  al.  2014) for ­various  patient conditions or body types to avoid hypothermia unless cooler temperatures are desired for other therapeutic effects. Equipment needed for aquatic therapy can include whirlpool tanks, swimming pools, or UWTMs and therapy type is selected based on the medical condition, patient outcome goals, and functional capabilities. Patient assistance during exercise varies, depending on the condition being rehabilitated. A floatation vest may be worn to provide additional buoyancy and balance, or lightweight harnesses can be used if less assistance is needed. Swimming and water-­walking exercises yield distinctly different results with joint motion and energy expenditures, but both provide therapeutic benefit. Swimming increases the overall total ROM in joint flexion and muscles are utilized differently

16.9  ­Therapeutic Exercise and Aquatic Therap

compared to activity on land. It can be beneficial for patients experiencing pain during joint extension or when joint extension is contraindicated and may be used until the patient starts to show improvement, then transitioned to water walking for gait patterning. Overall coordination, balance, and kinesthetic movement mechanisms are increased (Bates and Hanson  1996) with swimming, which may encourage early land walking for some patients. Active pool-­based exercise aims to improve muscle strength, aerobic fitness, flexibility, and overall ROM. In the early stages of therapy, the therapist assists and guides the patient to ensure appropriate limb movement and exercise is controlled. For example, some patients with weak limbs may need them to be cycled through the motion by the therapist to stimulate the neurological pathways associated with movement patterning (volitional limb movement) until strength and return of function occur (Egan and Fitzpatrick 2018). UWTM-­based exercise differs from swimming because many factors can be controlled to specifically address functional capabilities and joint extension. The UWTM allows for control of many factors like walking speed, duration, head and trunk position, and water depth. Water depth adjustments affect buoyancy and overall weight bearing on joints to alter the amount of strength required to move a limb through the water. If a patient is unable to stand unassisted or has difficulty moving a limb because of weakness, a therapist is needed to enter the UWTM exercise chamber with the patient to provide mechanical guidance during movement. Water depth effects experienced by dogs have been established in a study (Levine et al. 2010) and may be used to develop therapeutic protocols. Filling the UWTM to the patient’s hock joint reduces overall total weight bearing by only 9%, while a reduction of 62%

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Figure 16.17  Water depth affects overall weight bearing when immersed in water. A depth to the lateral malleolus of the tibia reduces body weight by approximately 91%; at the lateral condyle of the femur 85%; and at the level of the greater trochanter of the femur by 38%.

occurs at the hip joint near the Greater Trochanter (Figure 16.17). Initial aquatic exercise sessions should be based on current daily walking abilities or postoperative guidelines and progress to a moderate level to maintain overall health. In most cases, patients provide self-­guidance for the duration of swimming therapy; however, the therapist must gauge and plan for overall patient fatigue during every session by implementing frequent rest periods. Determination of ideal walking speed in an UWTM lacks supportive research for various gait patterns. In animal patients, overall leg length and stride length are used to determine the best walking speed; with smaller dogs often walking at faster speeds than larger dogs (Voss et  al.  2010) and adjusting the speed for the desired gait. Patients with weakness or paresis in the pelvic limbs may display a dissociative gait pattern where the forelimbs move at a faster tempo with shorter strides than in the rear limbs (Gordon-­Evans et  al.  2009) and therefore atypical walking speeds may need to be used.

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Appendix 16.A  Obtaining Goniometric Measurements in the Canine Patient Thoracic limbs

Shoulder

●● ●● ●● ●●

●●

Elbow

●● ●● ●● ●●

Carpus

●●

●● ●● ●●

●●

Normal flexion angle is 57°. Normal extension angle is 165°. The goniometer fulcrum is placed over the acromion process of the scapular spine. The base arm is placed over the point of insertion for the infraspinatus muscle following the scapular spine. The other is placed along the humeral shaft to the lateral epicondyle of the humerus. Normal flexion angle is 36°. Normal extension angle is 166°. The goniometer fulcrum is placed at the lateral aspect at the epicondyle of the humerus. One arm follows to the point of insertion of the infraspinatus muscle on the greater tubercle of the humerus and the other follows the line of the antebrachium to the ulnar styloid process. Normal flexion angle is 38° (the pads of the foot should comfortably touch the caudal aspect of the antebrachium). Normal carpal extension is 196° and is in slight hyperextension. The goniometer fulcrum is placed in the center of the joint. The arms along the axis of the long bones, one arm following metacarpal bones three and four and the other following the lateral humeral epicondyle. Varus (7°) and valgus (12°) angles may be measured by the long axes of the metacarpus and medial border of the radius with the carpal joint being placed in a medial or lateral position. Pelvic limbs

Hip

●● ●● ●● ●●

●●

Stifle

●● ●● ●● ●● ●●

Hock

●● ●● ●● ●● ●●

Normal flexion angle is 50°. Normal extension angle is 162°. The goniometer fulcrum is placed just proximal to the greater trochanter. The base arm of the goniometer forms a line to join the lateral femoral epicondyle of the femur and greater trochanter. The other arm forms a line joining the tuber sacrale and ventral border of the ilium (ischiadicum). Normal flexion angle is 41°. Normal extension angle is 162°. The goniometer fulcrum is placed near the lateral femoral condyle. The base arm follows the long axis of the tibial shaft to the lateral malleolus. The other arm follows a line to the greater trochanter along the lateral femoral condyle. Normal flexion angle is 38°. Normal extension angle is 165°. The goniometer fulcrum is placed at the lateral malleolus. The base arm following the long axis of the metatarsal bones three and four. The other arm along the long axis of the tibial shaft.

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Appendix 16.C  Postural Compensations and Associated Medical Conditions

Appendix 16.B  Limb Circumference Measurement location

Technique

Thigh girth (Millis et al. 1999)

●●

●●

●●

Gluteal and quadriceps

●●

Flexor/extensor musculatures of the antebrachium

●●

●● ●●

Deltoids

●●

Triceps

●●

Determine thigh length by measuring from the tip of the greater trochanter to the distal aspect of the lateral fabella. Circumference is determined at points equal to 70% of the thigh length beginning with the most proximal location. Limb position should be at a fairly neutral angle and not in full extension or flexion; causing muscle mass girth to change secondary to approximation or elongation (Millis et al. 2004). The tape measure device is placed snugly in the groin and wrapped to the lateral aspect of the thigh, meeting at the greater trochanter (Sprague 2018). Find a point 20% of the distance from the tip of the olecranon to the distal end of the styloid process of the ulna. Evaluate the proximal flexor and extensor musculatures. Joint effusion or conformational abnormalities may affect measurements in this location (Lorinson et al. 2019). The tape measurer is placed snugly in the axilla and wrapped to meet at the lateral aspect using the acromion process on the scapula as a landmark. At a point above the lateral epicondyle of the humerus where the triceps muscle group transitions into the tendon inserting onto the olecranon process of the ulna.

Appendix 16.C  Postural Compensations and Associated Medical Conditions Associated medical conditions ●● ●● ●●

Pelvic limb pain Pelvic limb weakness Spinal pain

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Common compensatory, postural, and movement changes: ●● ●● ●● ●● ●● ●● ●●

●● ●● ●● ●● ●● ●● ●● ●●

Staggered pelvic limb stance (cranial shift of a single pelvic limb) Sloped or kyphotic topline, lowered pelvic girdle Lowered head position Wide positioning of the forelimbs Inability to back up or turn sharply Hip “hike” or pelvic tilt Lameness at walk or trot (downward head bob when pelvic limb strikes the ground) Tendency to have pacing gait pattern Unable to scratch at the neck with a rear limb Unable to weight bear when loaded Preference for sitting or lying down Overuse of the tail for counterbalancing Leaning or resting against objects Avoidance of stairs, jumping, or weaving Unable to finish meals in one feeding (Continued )

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Associated medical conditions ●● ●●

Forelimb limb pain Neck pain

Common compensatory, postural, and movement changes: ●●

●● ●● ●● ●● ●● ●● ●● ●● ●●

Lameness at walk or trot (upward head bob when pelvic limb strikes the ground) Decreased cervical range of motion Scapular “hike” or dorsal displacement Abnormal shoulder posture (may be lateral or medial) Shifting weight to contralateral limb Unable to weight bear when loaded Prefers to lie down Difficulty jumping off objects Slipping with a thoracic limb when turning Unable to finish meals in one feeding

Appendix 16.D  Photobiomodulation Example Protocols Adapted from (Monici et al. 2019) Condition

Dose or energy density (J/cm2)

Acute analgesia – muscle

2–4

Chronic pain – muscle

4–8

Joint pain – acute

4–6

Joint pain – chronic

4–8

Osteoarthritis pain

8–10

Anti-­inflammatory acute and subacute

1–6

Anti-­inflammatory chronic

4–8

Degenerative nerve conditions

20

Appendix 16.E  Electrical Stimulation Example Protocols (Armitage 2019) TENS – acute pain

TENS – chronic pain

High frequency, low-­intensity

High intensity, low-­frequency

Hz (frequency): 50–150 pulses

Hz (frequency): 1–10 Hz

Pulse duration: 2–50 μs

Pulse duration: 100–400 μs

Amplitude: comfortable tingling level

Amplitude: high (set for visible muscle contractions)

Mechanism of action: gate control theory

Mechanism of action: release of endogenous endorphins

Treatment time: 20–30 minutes

Treatment time: 10–15 minutes (or prior to fatigue setting in)

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Appendix 16.G  Myofascial Trigger Point Examination Techniques

Appendix 16.F  Myofascial Trigger Point (MTrP) and Myofascial Pain Syndrome (MPS) Terminology Vocabulary

Description

Active MTrP

●●

Latent MTrP

●● ●●

Jump sign

●●

Local twitch response (LTR)

●●

Referral pain pattern

●●

Causes referral pain pattern at rest or in motion specifically for the muscle belly in which it is found Only painful when palpated Other characteristics of active MTrP may be similar Pain response to palpation that can be involuntary, wince, yelp, or withdraw in response to palpation Contraction of muscle fibers containing a trigger point with the contraction in fibers as a response to stimulation (snapping palpation or dry needling), involuntary in the transient muscle fibers MTrP creates pain felt at a distance, remotely from source (example: patient licks or bites an area distally, due to peripheral nerve or dermatome segment) and can be reproduced with palpation related to MTrP site of origin

Appendix 16.G  Myofascial Trigger Point Examination Techniques Palpation type

Description

Flat palpation

●●

Finger pressure is performed in the direction across the muscle fibers during compression against firm underlying structure.

Affected muscle groups ●● ●● ●● ●● ●●

Pincer palpation

●●

A grasp technique is used to hold the muscle between thumb and finger, rolling between until a taut band or bands are detected.

●● ●● ●● ●●

Snapping palpation

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●●

●●

●●

Similar to flat palpation and possibly more uncomfortable compared to other techniques. Helps to identify a local twitch response (LTR). Palpation with flat palpation technique over groups that would use pincer palpation. Once evident, muscle fibers are rolled transversely under the finger, then pulled back (similar to plucking guitar string) while keeping firm contact with the surface directly over the MTrP.

●● ●● ●● ●●

Latissimus dorsi Deltoideus Supraspinatus Infraspinatus Serratus ventralis Sartorius Gastrocnemius Triceps Quadriceps Tensor fascia latae Gluteals Biceps Paraspinals

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Appendix 16.H  Techniques Addressing Myofascial Trigger Points Noninvasive techniques

Ischemic compression

●●

●●

Static stretch Positional release technique Low-­level-­laser therapy

●●

●●

●● ●● ●●

Therapeutic ultrasound

●● ●●

Transcutaneous electrical nerve stimulation Extracorporeal shockwave therapy

●● ●●

●● ●●

Hold over MTrP and increase pressure for 20 seconds. Release for 15–20 seconds, then repeat at 30 seconds to 90 s until reduction of jump sign or LTR is noted. Blanches tissue when compressed, hyperaemic when pressure released. Stretch is applied to warmed muscle 15–20 seconds; relax and then apply ischemic compression. Ischemic compression applied over MTrP and shorten muscle length; hold for up to 90 seconds. Used directly over MTrP. Energy dose 4–6 J/cm2. Can be used along muscle spasm or band with MTrP. Used to relieve muscle spasms. Sample protocol: 5 minutes, pulsed 20%, 1 or 3 MHz depending on depth of muscle and MTrP. Used for MPS in humans. Sample protocol: 100 Hz, 250 ms stimulation, followed by 100 Hz, 50 ms. Used for MPS and MTrP in humans. Sample protocol: 800–1000 pulse delivery; energy level: 0.25 mJ/mm2; frequency of 4–6 Hz; 1–2 treatments per week for total of 3–7 treatments. Invasive techniques

Dry needling

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Injection: Local anesthetic ●● Corticosteroids ●● Botulinum toxin

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Performed by trained veterinarian or acupuncturist. Elicits a LTR, then continues to engage needle to reproduce symptomatology until relief is noted. Small doses, controlled manner, prevention of local soreness (procaine and lidocaine). Controls local inflammatory response. Dangers of local myotoxicity. Relaxes an overactive muscle blocking acetylcholine, though nondiscriminatory of TPs and motor endplates (must localize MTrP first)

Appendix 16.I  Joint Mobilizations Grade 1 Joint mobilization

Small amplitude movements with 3–4 oscillations per second

Grade 2 Joint mobilization

Large amplitude movements with 3–4 oscillations per second

Grade 3 Joint mobilization

Large amplitude movements with 3–4 oscillations per second at END of range of restricted motion

Grade 4 Joint mobilization

Small amplitude movement with 3–4 oscillations per second between point of resistance in range of motion and the resistance felt at end of PROM

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Appendix 16. J  Passive Range of Motion  

Appendix 16.J  Passive Range of Motion Description ●●

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One hand is placed on the affected limb above the joint and the other hand below the joint. The entire limb should be supported to avoid unnecessary stress on involved joints. Slowly flex and extend the most proximal joint of the limb in a slow, rhythmic fashion maintaining neutral positioning of the remaining joints of the limb. The degree of flexion and extension achieved depends on patient comfort and the condition being treated. Keeping hand positioning the same, move to the next joint distal to the one in the beginning of the sequence. It is important to stabilize the joint above the segment being exercised to separate certain joint motions. Each joint should be addressed, including the digits. While supporting the entire limb, the entire limb is abducted about 5° and held in a mild sustained stretch.

Joint

Flexion

Extension

Hip

Stifle

Hock

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Joint

Flexion

Extension

Shoulder

Elbow

Carpus

Appendix 16.K  Therapeutic Massage Techniques Hold

Static placement of the hands on the animal’s body at the beginning and completion of a massage therapy session. Used to introduce touch to the animal.

Stroking

A medium to light pressure, similar to “petting.” Aides in relaxation and allows for assessment of tissues, muscle tone, swelling, masses, and temperature differences. Slow, long movements sedate the patient while faster, shorter movements stimulate. Stroking is used at the beginning and end of the massage after a hold.

Effleurage (“to skin lightly”)

A medium pressure producing small “rolls” or “waves” of skin folding in front of the fingertips in the direction of muscle fibers. The skin is allowed to glide gently over the underlying fascia to reduce adhesions. Effleurage is often used in between techniques as a transition technique. Effleurage functions to move fluid to lymph nodes, aid drainage, improve mobility between tissues, and decrease muscle tone.

Petrissage (“to knead”)

Rolling, lifting, kneading, or compression of the muscle bellies. Petrissage promotes muscle relaxation, decreases stiffness, increases blood flow, improves length of fibrous tissue, and increases scar tissue mobility.

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Appendix 16.L  Therapeutic Exercises for Early Rehabilitation

Appendix 16.L  Therapeutic Exercises for Early Rehabilitation Exercise

Description

Balance or rocker board

Patient is assisted to stand in square posture and gently rock equipment to initiate muscle contraction. Assistive aides are used to position and support the patient as needed.

Peanut shaped or physioballs

Inflated air equipment aids weak patients in a standing position. Equipment can be centered under the patient’s body, under the chest and forelimbs, or under the chest and hindlimbs. Patients can also lie down, sit, or stand on the ball. Therapists should always stabilize equipment to prevent injury.

Foam or cushions

Depending on strength level, patients can walk over equipment, stand and perform balancing or weight shifting activities, and perform common behavior techniques (sit, down to sit, etc.).

Passive range of motion

In a relaxed position and lying down; the therapist guides one joint at a time through joint motion. Activation of muscles or pain should not occur.

Bicycling or continuous passive range of motion

In a relaxed position lying down; the therapist guides the entire limb through a gait cycle. This exercise is especially useful for nonambulatory patients. If the patient is able to stand, the limb may be cycled to include the paw pads contacting the ground for increased proprioception.

High five or front paw shake

Promotes range of motion in the forelimb, increased loading of contralateral limb, and proprioception. Patients may perform the activity in sitting or standing position (if strength is present). Therapists may lift a front paw if needed to help shape the behavior in early stages.

Stationary standing

Used to reestablish mobility for the severely disabled. Assisted standing is used for patients prior to active exercise activity. Once balance improves, patients may perform this exercise on a foam pad.

Stationary standing with weight shifting

Therapists gently rock patients to initiate gentle muscle contraction and sensory stimulation. As strength and balance increase, gentle pushing techniques can be used and pressure may be released more rapidly.

Rhythmic stabilization and bouncing

Used to promote peripheral proprioception and neuromuscular stimulation by increasing loading on cartilage, ligaments, tendons and musculature. Therapists may place pressure over shoulders or hips in rhythmic motions to “compress” the limb when patients are standing, sitting, or lying down. Therapy should progress from firm to more unstable surfaces as strength increases.

Active weight shifting

Patients should stand if possible but can be sitting or lying down. When standing, assistive aids should be used when necessary. Food is used to lure the patient’s head in varying directions to encourage weight shifting. Ideally, feet stay in a stationary position.

Elevated forelimb standing

Increases weight and loading placed on pelvic limbs. Provides mild stretching to hip flexors, depending on the height of the elevated surface.

Elevated hindlimb standing

Increases weight and loading placed on thoracic limbs. Provides mild stretching to caudal thigh muscle when the patient’s head is lowered, depending on the height of the elevated surface.

Three-­leg standing

Well suited for sensory neuromuscular disorders or generalized weakness. Patients should not be falling over and supported when balancing. Duration of balancing can range from one (1) to twenty-­five (25) seconds. Limbs should not be abducted.

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Exercise

Description

Walking

One of the most important exercises for patients. In early stages assistive devices should be used to prevent compensation. Speed of walking is increased incrementally and started on flat surfaces. As strength and mobility increases, walking surfaces can change (e.g. sloped angles, mattress or foam, sand, or gravel). Promotes limb loading, gait patterning, improves strength, endurance, balance, and proprioception.

Backwards walking

Increases hindlimb loading, range of motion, activation of caudal musculatures, and coordination of limbs. Patients with moderate weakness will require assistance.

Stair climbing

Promotes range of motion and joint function. Requires balance, proprioception, and strength. Weak patients may need assistive devices to prevent injury. Performing activity over shorter flights (3–4 steps) increases exercise quality. Smaller patients may need modifications. Platforms placed in a line may be used as an alternative for smaller or weaker patients.

Sit to stand and down to stand

Strengthens the rear leg muscles of the hips, stifle, and tarsal joints when sitting and standing. Promotes limb loading. Modifications such as using assistive aides or sitting on cushions may be necessary depending on patient strength and joint motion. Down to stand exercise promotes strength, coordination, and balance. Ideal sitting and down posture should be with rear limbs squarely under the pelvis.

Crawling or tunnels

Promotes overall limb loading and range of motion in flexion. Strengthens muscles surrounding joints. Not to be used when loading of major joints in flexion is not desired. Height affects overall joint flexion. Length of crawling affects difficulty level.

Cavaletti rails

Range of motion and joint function, limb loading, proprioception and balance; activates atrophied muscles, core and back flexor muscles. Height of rail, distance, and number of rails affect joint motion and stride length. Speed of exercise should encourage limb use and not avoidance.

Weaving and figure eight’s

Encourages spinal range of motion, balance, proprioception and joint motion. Requires strength and balance. Objects placed closer together will encourage increased spinal bending.

Appendix 16.M  Sample Guidelines Congenital conditions

Considerations

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Therapeutic goals

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Patients may have varying degrees of disability or dysfunction Conditions can include angular limb deformities (ALD), malformations in vertebral segments or agenesis of limbs. The size of the patient and intended living environment may dictate interventions needed to support daily activities of living Preservation of joint motion and flexibility Maintenance of muscle mass; preserve function and strength in unaffected bodily regions (e.g. preserve forelimb strength if the hindlimbs or spine is affected). Nutritional guidance to maintain ideal body weight.

Appendix 16.M  Sample Guidelines

Congenital conditions

Therapeutic recommendations

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Joint Health: Nutraceuticals, chondroprotectants, disease modifying anti-­inflammatory drugs, polysulfated glycosaminoglycans, anti-­myostatin supplementation Regenerative medicine and biologics. Nutrition: Maintenance of ideal body condition. Manual therapy: Therapeutic massage; myofascial trigger point Aquatic therapy: UWTM, swimming Physical, thermal, and electrical agents: varies depending on condition. Goals are to reduce pain and inflammation. Therapeutic exercise: Preservation of daily activities of living and independence; flexibility, proprioception and balance; leash walks. Environmental modifications: Traction aids for flooring; restricting access to stairs or furniture if patient is disabled. Assistive devices: Orthotics, prosthetics, or mobility carts can provide support for independent activity. Emotional health support: Provide as needed for activity management with or without other animals. Client communication: Long-­term outcome management of conditions. Orthopedic conditions

Considerations

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Therapeutic goals

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Therapeutic recommendations

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Conditions may be acquired over time, such as in degenerative joint disease or occur acutely from trauma. Long-­term joint health, including range of motion and reduction of inflammation, helps maintain overall mobility and reduces pain. Depending on the condition, activity modifications may be long term or temporary, especially if surgery is necessary. Younger animals may not develop behavioral communication and coping skills due to activity restrictions during healing. Long-­term activity modification typically includes low-­impact, short-­ duration activity. Preservation of joint motion and flexibility. Maintenance of muscle mass. Utilize assistive devices, orthotics, prosthetics, or mobility carts to provide support for activity goals, depending on life stage. Provide nutritional guidance to maintain ideal body weight. Joint health: Nutraceuticals, chondroprotectants, disease modifying anti-­inflammatory drugs, polysulfated glycosaminoglycans, anti-­myostatin supplementation. Regenerative medicine and biologics. Manual therapy: PROM to affected joints; therapeutic massage; myofascial trigger point therapy. Aquatic therapy: UWTM, swimming. Physical, thermal, and electrical agents: TENS; Photobiomodulation, Extracorporeal shockwave, PEMF Therapeutic exercise: spinal flexibility bending, three-­leg standing, sit-­to-­stand, down-­to-­stand, down-­to-­sit, weight shifting (elevated front or rear; level or unstable surface depending on disability), progressive activity to reintroduce stairs or ramps; land treadmill gait patterning. (Continued )

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Orthopedic conditions

Therapeutic recommendations

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Environmental modifications: Use bedding in sleeping areas that is firm and does not “bottom out” when pressed on; Place nonslip runners in front of recovery areas to prevent falls in sedated patients. Utilize nonslip or firmly padded surfaces during procedures such as venipuncture, nail trims, and other procedures performed by the veterinary support team. Utilize positioning aids such as foam rollers, wedges, and bolsters to improve postural positioning when recovering. Assistive devices: Use abdominal support or harness (thoracic, pelvic, or two-­point) to prevent injury and support movement. Emotional health support: Provide enrichment during the postoperative healing periods and anxiety-­reducing interventions. Client communication: Inform of long-­term activity guidelines (low-­ impact); pharmaceutical side effects and interactions, joint supplementation, emotional health support. Neurological conditions

Considerations

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Therapeutic goals

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Therapeutic recommendations

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Conditions may be degenerative or acute and cause varying degrees of disability. Conditions may cause permanent disability and loss of function. Owner understanding of disease management and nursing care helps improve patient quality of life and emotional health support. Preservation of joint motion, flexibility. Maintenance of muscle mass; preserve function and strength in unaffected bodily regions (e.g. preserve forelimb strength if the hindlimbs or spine is affected). Utilize assistive devices, orthotics, prosthetics, or mobility carts provide support for activity. Joint health: Nutraceuticals, chondroprotectants, disease modifying anti-­inflammatory drugs, polysulfated glycosaminoglycans, anti-­myostatin supplementation. Regenerative medicine and biologics. Nutrition: Promote ideal body condition score. Manual therapy: PROM; CPROM; therapeutic massage; myofascial trigger point therapy. Aquatic therapy: Assist UWTM, assist with swimming. Physical, thermal, and electrical agents: photobiomodulation, electrical stimulation (TENS, NMES); thermal therapy, PEMF. Therapeutic exercise: Assist with standing, promote flexibility. Encourage independent daily activities of living, weight shifting, gait training, balance, and proprioception. Environmental modifications: Traction flooring aides; padded bedding that does not “bottom” out when patient lays down; accessible food and water; restricted access to stairs. Utilize ramps and stairs for furniture and vehicles. Assistive devices: Provide slings; harnesses; protective footwear, toe-­up devices to help in foot placement. Emotional health support: Utilization of anxiety reducing supplements. Client communication: Provide information on disability and pain scoring; nursing management of disabled animals (toileting, skin care, access to food/water); emotional health monitoring.

Appendix 16.M  Sample Guidelines

Aging and disability

Considerations

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Therapeutic goals

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Therapeutic recommendations

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Disability occurs gradually in aging patients with accommodation measures implemented later in life. Early introduction of management strategies can increase success for patients and owners. The acutely disabled patient may require a longer period of acclimation and support; emotional health of the animal should be continuously assessed. Cognitive impairment or dysfunction may be present. Patients needing veterinary care may need special handling and precautions under anesthesia, including positioning of limbs, transportation support of the vertebral column while anesthetized, and positioning for procedures that require changes in body position. Every precaution should be taken to not worsen mobility upon recovery. Preservation of joint motion and flexibility. Maintenance of muscle mass; preserve function and strength in unaffected bodily regions (e.g. preserve forelimb strength if the hindlimbs or spine is affected). Utilize assistive devices, orthotics, prosthetics or mobility carts provide support for activity. Joint health: Nutraceuticals, chondroprotectants, disease modifying anti-­inflammatory drugs, polysulfated glycosaminoglycans, anti-­myostatin supplementation. Regenerative medicine and biologics. Nutrition: Maintenance of body mass. Manual therapy: PROM; therapeutic massage. Aquatic therapy: Assisted and guided swimming; UWTM. Physical, thermal, and electrical agents: Provide heat or cryotherapy; photobiomodulation; TENS or NMES. Therapeutic exercise: –– Spinal flexibility stretching (“cookie stretches”) –– Pole step walking at slow speeds –– Elevated front-­leg weight shifting (if able to stand) –– Weight-­shifting in sagittal, transverse, median planes –– Sit-­to-­stand (assisted as needed), push-­ups Environmental modifications: Bedding in recovery areas that is firm and does not “bottom out” when pressed on; nonslip runners in front of recovery areas to prevent falls in sedated patients; positioning aids such as foam rollers, wedges and bolsters to improve postural positioning when recovering; nonslip or firmly padded surfaces during procedures such as venipuncture, nail trims, and other procedures performed by the veterinary support team. Assistive devices: slings and harnesses or transport gurneys can prevent injury to patients and the veterinary team during transport. Emotional health support: consider pharmaceuticals or supplements to assist with anxiety or cognitive dysfunction; enrichment activities. Client communication: Provide support during the aging process. (Continued )

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Critically ill and hospitalized

Considerations

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Therapeutic goals

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Therapeutic recommendations

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Treatments are performed with a “cluster care” strategy to minimize disruptions to allow patients needed rest and medical treatments. –– Cluster care is the combination of medical treatment delivery (e.g. obtaining a TPR) immediately followed by prescribed therapeutic treatments (e.g. PROM, PBM) to reduce patient disruption while hospitalized. Application of treatment plan is provided only to accessible bodily regions and should not disrupt medical interventions (e.g. catheters, bandaging, wounds). Unstable fractures, infectious disease, hemorrhage, neoplastic conditions, unmanaged wounds, and severe aggression are contraindicated for treatments. Preservation of joint health. Attenuation of muscle therapy. Postural support to facilitate cardiovascular and lymphatic health. Prevention of decubitus ulcerations. Nursing care for feeding, elimination, and emotional health. Joint and muscle health: not indicated. Nutrition: must meet daily energy requirements for condition being managed; some patients may be withheld food. Manual therapy: PROM; CPROM; lymphatic massage. Aquatic therapy: contraindicated. Physical, thermal, and electrical agents: Thermal therapy, electrical stimulation (NMES or TENS), PEMF, photobiomodulation. Therapeutic exercise: Standing therapy, weight shifting, postural positioning. Environmental modifications: foam wedges for postural and respiratory support; foam wedges or bolsters to support circulation of limbs; absorptive bedding. Assistive devices: Slings, harnesses (single-­point, two-­point). Emotional health support: Cognitive awareness may vary; enrichment activities to support long-­term hospitalizations. Client communication: patient care and progress updates. Palliative, hospice care and oncology

Considerations

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Therapeutic goals

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Patient diseases are progressive and terminal. Multiple comorbidities may be present requiring management. Preservation of joint motion and flexibility. Preservation of emotional health and human-­animal bond. Nursing care to maintain skin health and toileting needs. Maintenance of muscle mass; preserve function and strength. Utilize assistive devices, orthotics, prosthetics, or mobility carts provide support for activity.

­Reference

Palliative, hospice care and oncology

Therapeutic recommendations

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Joint and muscle health: may not be necessary, depending on the condition and patient but consider nutraceuticals, chondroprotectants, essential fatty acids, polysulfated glycosaminoglycans, and vitamins; anti-­myostatin supplements. Pharmaceuticals: Varies depending on the condition and polypharmacy interactions. Nutrition: May require appetite stimulants, balanced to provide support for condition. Manual therapy: PROM, CPROM, therapeutic massage, myofascial trigger point therapy. Aquatic Therapy: Assisted standing in UWTM, assisted/guided swimming (for relaxation or to provide aquatic manual therapy). Physical, thermal, and electrical agents: PEMF, TENS, heat therapy for painful body regions (so as not to exacerbate the condition). Therapeutic exercise: Activities to support daily activities of living (DAL) and postural strength, sitting and lying down squarely, spinal bending stretched, weight shifting. Environmental modifications: Flooring traction aides, use of multiple bedding options, restricting stair access; foam wedges for postural support, absorptive bedding. Assistive devices: Use of animal strollers, slings, and harnesses, standing aides, wheelchairs. Emotional health support: Enrichment for mental stimulation; provide quiet areas of the house away from traffic. Client communication: End of life care and grief counseling, nursing case, including bowel, bladder, and skin integrity management, pain assessment, and management.

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K. Wittel, D. Levine, et al.), 289. Germany: VetVerlag, Buchhandel und Seminar GmbH (VBS). Aulakh, K.S., Lopez, M.J., Hudson, C. et al. (2021). Prospective clinical evaluation of intra-­articular injection of Tin-­117m (117mSn) radiosynoviorthesis agent for Management of Naturally Occurring Elbow Osteoarthritis in dogs: a pilot study. Veterinary medicine (Auckland, N.Z.) 12: 117–128. https://doi.org/10.2147/VMRR.S295309. Bartner, L. (2020). The neurological exam. In: Canine Lameness, 1e (ed. F. Duerr), 56. Wiley-­Blackwell. Bates, A. and Hanson, N. (1996). Aquatic Exercise Therapy. Philadelphia: Saunders. Bellows, J., Colitz, C.M.H., Daristotle, L. et al. (2015). Common physical and functional

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Physical Education and Rehabilitation Journal 11 (21): 36–43. https://doi.org/10.2478/tperj-­ 2018-­0014. Goldberg, M.E. (2018). Introduction of physical rehabilitation for veterinary technicians/ nurses. In: Physical Rehabilitation for Veterinary Technicians and Nurses (ed. M.E. Goldberg and J.E. Tomlinson), 8. Wiley. Goldberg, M.E. and Tomlinson, J.E. (2018). The disabled patient 1: assistive devices and technology. In: Physical Rehabilitation for Veterinary Technicians and Nurses, 1e (ed. M.E. Goldberg and J.E. Tomlinson), 148–150. Wiley. Goldston, R.T. (1995). Introduction and overview of geriatrics. In: Geriatrics and Gerontology of the Dog and Cat (ed. R.T. Goldston and J.D. Hoskins), 1–8. Philadelphia, PA: WB Saunders. Gordon-­Evans, W.J., Evans, R.B., Knap, K.E. et al. (2009). Characterization of spatiotemporal gait characteristics in clinically normal dogs and dogs with spinal cord disease. American Journal of Veterinary Research 70: 1444–1449. Grassi, A., Quaglia, A., Canata, G.L., and Zaffagnini, S. (2016). An update on the grading of muscle injuries: a narrative review from clinical to comprehensive systems. Joints 4 (1): 39–46. https://doi.org/10.11138/jts/ 2016.4.1.039. Gross, D.M. (2002). Introduction to small animal physical therapy. In: Canine Physical Therapy – Orthopedic Physical Therapy (ed. R.M. Woodman), 7–11. Connecticut: Wizard of Paws. Gross-­Saunders, D., Walker, R.J., and Levine, D. (2014). Joint mobilizations. In: Canine Rehabilitation and Physical Therapy, 2e (ed. D.L. Millis and D. Levine), 447–451. Henderson, A. and Millis, D.L. (2014). Tissue healing: tendons, ligaments, bone, muscle and cartilage. In: Canine Rehabilitation and Physical Therapy, 2e (ed. D.L. Millis and D. Levine), 80, 86. Hielm-­Bjorkman, A.K., Kuusela, E., Liman, A. et al. (2003). Evaluation of methods for assessment of pain associated with chronic

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osteoarthritis in dogs. Journal of the American Veterinary Medical Association 222: 1552–1558. Hourdebaigt, J.P. (2004). Canine Massage – A Complete Reference Manual, 2e, 46. Dogwise Publishing div. of Direct Book Service, Inc. Hudson, J.T., Slater, M.R., Taylor, L. et al. (2004). Assessing repeatability and validity of a visual analogue scale questionnaire for use in assessing pain and lameness in dogs. American Journal of Veterinary Research 65: 1634–1643. Hutchinson, D., Sutherland-­Smith, J., Watson, A.L., and Freeman, L.M. (2012). Assessment of methods of evaluating sarcopenia in old dogs. American Journal of Veterinary Research 73 (11): 1794–1800. Jaegger, G., Marcellin-­Little, D.J., and Levine, D. (2002). Reliability of goniometry in Labrador retrievers. American Journal of Veterinary Research 63: 979–986. Jurek, C. (2013). The role of physical manipulation (chiropractic) in canine rehabilitation. In: Canine Sports Medicine and Rehabilitation (ed. M.C. Zink and J. Van Dyke), 427–446. Hoboken, NJ: Wiley. Kafa, N., Citaker, S., Omeroglu, S. et al. (2015). Effects of kinesiologic taping on epidermal– dermal distance, pain, edema, and inflammation after experimentally induced soft tissue trauma. Physiotherapy Theory and Practice 31 (8): 556–561. https://doi-­org.ezproxy. simmons.edu/10.3109/09593985.2015.1062943. Levine, D., Rittenberry, L., and Millis, D.L. (2004). Aquatic therapy. In: Canine Rehabilitation & Physical Therapy (ed. D.L. Millis, D. Levine, and R.A. Taylor), 264–275. St Louis: Saunders. Levine, D., Marcellin, D.J., Millis, D.L. et al. (2010). Effects of partial immersion in water on vertical ground reaction forces and weight distribution in dogs. American Journal of Veterinary Research 71: 1413–1416. Liu, S. et al. (1995). Collagen in tendon, ligament, and bone healing. Clinical Orthopaedics 318: 265–278. Lorinson, K., Lorinson, D. et al. (2019). Examination of the physiotherapy patient. In: Essential Facts of Physical Medicine, Rehabilitation and Sports Medicine in

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Companion Animals (ed. B. Bockstahler, K. Wittel, D. Levine, et al.), 91. Germany: VetVerlag, Buchhandel und Seminar GmbH (VBS). Marcellin-­Little, D.J. et al. (2015). Logistics of companion animal rehabilitation. The Veterinary Clinics of North America. Small Animal Practice 35) Elsevier-­Saunders: 1473–1484. Marcellin-­Little, D.J., Levine, D., and Millis, D.L. (2021). Multifactorial rehabilitation planning in companion animals. Advances in Small Animal Care 2: 1–10. Elsevier. https://doi.org/10.1016/j.yasa.2021.06. 0012021. McDonald, J.W. and Sadowsky, C. (2002). Spinal-­cord injury. Lancet 359: 417–425. Melzack, R. and Wall, P.D. (1965). Pain mechanisms: a new theory. Science 150 (3699): 971–979. Millard, R. (2014). Exercise physiology of the canine athlete. In: Canine Rehabilitation and Physical Rehabilitation (ed. D.L. Millis and D. Levine), 163–165. Elsevier. Miller, L. (2000). Breakthroughs. Veterinary Forum (Aug): 11. Millis, D.L., Scroggs, L., and Levine, D. (1999). Variables affecting thigh circumference measurements in dogs. In: Proc 1st Int Symp Rehab Physical Ther Vet Med, 157. Millis, D.L., Lewelling, A., and Hamilton, S. (2004). Range-­of-­motion and stretching exercises. In: Canine Rehabilitation & Physical Therapy (ed. D.L. Millis, D. Levine, and R.A. Taylor), 431. St Louis, MO: Saunders. Monici, M., Millis, D., Ciuperca, I., and McCarthy, D. (2019). Essential facts of physical medicine. In: Rehabilitation and Sports Medicine in Companion Animals (ed. B. Bockstahler, K. Wittel, D. Levine, et al.), 252. Germany: VetVerlag, Buchhandel und Seminar GmbH (VBS). Mucha, M. and Millis, D. (2019). Extracorporeal shock wave therapy. In: Essential Facts of Physical Medicine, Rehabilitation and Sports Medicine in Companion Animals (ed. B. Bockstahler, K. Wittel, D. Levine, et al.).

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Germany: VetVerlag, Buchhandel und Seminar GmbH (VBS). Nganvongpanit, K., Tanvisut, S., Yano, T. et al. (2014). Effect of swimming on clinical functional parameters and serum biomarkers in healthy and osteoarthritic dogs. ISRN Veterinary Science 459809. https://doi.org/ 10.1155/2014/459809. Nicolson, A., Moir, L., and Millsteed, J. (2012). Impact of assistive technology on family caregivers of children with physical disabilities: a systematic review. Disability and Rehabilitation. Assistive Technology 7 (5): 345–349. Norkin, C.C. and White, D.J. (1995). Measurement of Joint Motion. A Guide to Goniometry, 2e. Philadelphia: FA Davis. Pilla, A., Fitzsimmons, R., Muehsam, D. et al. (2011). Electromagnetic fields as first messenger in biological signaling: application to calmodulin-­dependent signaling in tissue repair. Biochimica et Biophysica Acta 1810 (12): 1236–1245. https://doi.org/10.1016/ j. bbagen.2011.10.001. Prato, F.S., Carson, J.J., Ossenkopp, K.P., and Kavaliers, M. (1995). Possible mechanisms by which extremely low frequency magnetic fields affect opioid function. The FASEB Journal 9 (9): 807–814. https://doi.org/ 10.1096/fasebj.9.9.7601344. Reid, J., Nolan, A.M., and Scott, E.M. (2018). Measuring pain in dogs and cats using structured behavioural observation. The Veterinary Journal 236: 72–79. ISSN: 1090-­0233. https://doi.org/10.1016/j.tvjl. 2018.04.013. Riegger-­Krugh, C., Millis, D.L., and Weigel, J.P. (2014). Canine anatomy. In: Canine Rehabilitation and Physical Therapy, 2e (ed. D.L. Millis and D. Levine), 41–78. Sato, N.Y.S., Bastos, B.B.B., Pereira, M.A.A. et al. (2020). Myofascial pain syndrome, myofascial trigger points and trigger points in veterinary medicine: a review. Brazilian Journal of Veterinary Research and Animal Science 57 (2): e164351. https://doi.org/10.11606/issn.1678-­ 4456.bjvras.2019.164351.

­Reference

Savvidou, O., Milonaki, M., Goumenos, S. et al. (2019). Glucocorticoid signaling and osteoarthritis. Molecular and Cellular Endocrinology 480: 153–166. Sherwood, J.M., Roush, J.K., Armbrust, L.J., and Renberg, W.C. (2017). Prospective evaluation of intra-­articular dextrose prolotherapy for treatment of osteoarthritis in dogs. JAAHA 53: 135–142. Simons, D.G. and Dommerholt, J. (2006). Myofascial trigger points and myofascial pain syndrome: a critical review of recent literature. The Journal of Manual & Manipulative Therapy 14 (4): 125E–171E. http://dx.doi.org/10.1179/jmt.2006. 14.4.125E. Sims, C., Waldron, R., and Marcellin-­Little, D.J. (2015). Rehabilitation and physical therapy for the neurologic veterinary patient. The Veterinary Clinics of North America. Small Animal Practice 45: 123–143. Sprague, S. (2018). Introduction to canine rehabilitation. In: Canine Sports Medicine and Rehabilitation, 2e (ed. M.C. Zink and J.B. Van Dyke), 89. Ames, IA: Wiley-­Blackwell. Stark, H., Fischer, M.S., Hunt, A. et al. (2021). A three-­dimensional musculoskeletal model of the dog. Scientific Reports 11: 11335. https://doi.org/10.1038/s41598-­021-­90058-­0. Styles, S. and Einhorn, T. (1997). Fracture healing and responses to skeletal injury. In: Principles of Orthopaedic Practice (ed. R. Dee, L.C. Hurst, M.A. Gruber, and S.A. Kottmeier). New York: McGraw-­Hill. Sutton, A. (2004). Massage. In: Canine Rehabilitation & Physical Therapy (ed. D.L. Millis, D. Levine, and R.A. Taylor), 303–309. St Louis: Saunders, 317. Tnibar, A., Persson, A.B., and Jensen, H.E. (2017). Mechanisms of action of an intraarticular 2.5% polyacrylamide hydrogel (Arthramid Vet) in a goat model of

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osteoarthritis: preliminary observations. Journal of Biomedical Engineering 3 (4): 1022. Travell, J.G. and Simons, D.G. (1983). Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore: Williams & Wilkins. Vishwanath, K., McClure, S.R., and Bonassar, L.J. (2023). Polyacrylamide hydrogel lubricates cartilage after biochemical degradation and mechanical injury. Journal of Orthopaedic Research 41 (1): 63–71. https://doi.org/10.1002/ jor.25340. Epub 2022 Apr 20. PMID: 35384042. Voga, M., Adamic, N., Vengust, M., and Majdic, G. (2020). Stem cells in veterinary medicine-­ current state and treatment options. Frontiers in Veterinary Science 7: 278. Voss, K., Galeandro, L., Wiestner, T. et al. (2010). Relationships of body weight, body size, subject velocity, and vertical ground reaction forces in trotting dogs. Veterinary Surgery 39 (7): 863–869. Wall, R. (2014). Introduction to myofascial trigger points in dogs. Topics in Companion Animal Medicine 29 (2): 43–48. https://doi. org/10.1053/j.tcam.2013.11.001. Epub 2014 Feb 12. PMID: 25454375. Wiese, A.J. (2015). Assessing pain. In: Handbook of Veterinary Pain Management, 3e (ed. J.S. Gaynor and W.W. Muir), 84–85. St. Louis, MO: Elsevier. Wittek, K. and Bockstahler, B. (2019). Active therapeutic exercises. In: Essential Facts of Physical Medicine, Rehabilitation and Sports Medicine in Companion Animals (ed. B. Bockstahler, K. Wittel, D. Levine, et al.), 119. Germany: VetVerlag, Buchhandel und Seminar GmbH (VBS). World Health Organization (1997). International Classification of Diseases, 9e. New York: WHO. Zink, C.M. (2013). Locomotion and athletic performance. In: Canine Sports Medicine and Rehabilitation (ed. C.M. Zink and J.B. Van Dyke), 20. Ames, IA: Wiley-­Blackwell Publishing.

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17 Nutrition and Integrative Medicine Robin Saar1, Jaime Brassard2, and Stephen Niño Cital3 1

Royal Canin, Lethbridge, Alberta, Canada Canadian Association of Veterinary Cannabinoid Medicine (CAVCM), Whitehorse, Yukon Territory, Canada 3 Howard Hughes Medical Institute at Stanford University, Remedy Veterinary Specialists, and Veterinary Anesthesia Nerds, LLC., San Francisco, CA, USA 2

In veterinary medicine, nutrition is one area that affects every pet that comes into the hospital. Out of the three components that influence the life of an animal – genetics, environment, and nutrition – nutrition is the one factor that the veterinary healthcare team, specifically veterinary technicians, or technologists, can affect (Kirk 2011). Nutraceutical and animal supplements have been used to help treat pain since humans started domesticating animals. While some of these approaches do indeed provide clinically significant benefit, many do not provide any benefit and could even be considered harmful. Despite an overwhelming amount of evidence disproving, or not supporting the use of various products or techniques there is an ever-­ growing interest in herbal (plant-­based medicine) and holistic approaches in veterinary healthcare. In this chapter we encourage the use of nutraceuticals and animals supplements as an integrative approach, where we combine conventional veterinary medicine with herbal or holistic approaches. From an ethical and evidence-­based medicine approach we have only included therapies that have at least some scientific basis for clinical use.

17.1  ­Nutrition – The 5th Vital Assessment When completing a full evaluation of a pet’s health, there are parameters that veterinary professionals routinely assess and record in the medical record. For over 30 years, temperature, pulse, and respiration (TPR) parameters were the minimal assessments required. Prior to the 2000s, the administration of analgesics post “routine surgeries” was considered “optional.” Veterinary professionals began to recognize the importance of pain management, introducing pain as the fourth vital assessment by AAHA in the late 1990s (Cline et al. 2021). Understanding that health is a reflection of genetics, environment, and nutrition, WSAVA published guidelines for the fifth vital assessment in 2010 (Kirk 2011). This standardized assessment brings awareness to the importance of nutritional assessments in every patient evaluation completed by veterinary professionals, along with resources to help identify the association between nutrition and disease. These assessments help veterinary professionals with the ability to develop

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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­ utrition protocols and provide sound recomn mendations for pets using evidence-­based medicine (Kirk 2011).

17.1.1  Components of a Nutrition Assessment AAHA developed a three-­part approach to the nutritional component of the assessment: (i) pet-­related components such as age, physiological status (body condition score [BCS], muscle condition scoring [MCS]), and activity level; (ii) diet-­related components, including the appropriateness for the pet’s life stage or disease state, any safety concerns, and nutrient inclusion of the diet; and (iii) the feeding management of the diet, which encompasses the method of feeding (free choice, meal fed, etc.), the frequency and timing of meals, the location and type of feeding dish, and any environmental factors that may play a role (multiple pets in the home, children, housing, and season) (Cline et al. 2021). It is important for the technician to take a thorough history and ask open-­ended questions that may help uncover otherwise overlooked signs. Using sentences that start with “tell me about…,” or “describe…” will encourage pet parents to recall and share. 17.1.1.1  Pet-­Related Components

The most practical method of assessing body composition is the BCS. The BCS is a subjective assessment of an animal’s body fat that considers the animal’s frame size independent of its weight. A variety of scoring systems with defined criteria have been published. All are useful tools for assessing body composition. In addition to body weight, body composition should always be documented at every exam. Body weight alone does not indicate how appropriate the weight is for an individual animal. The BCS puts body weight in perspective for each individual patient. MCS is an assessment of metabolic health to ensure the pet is not utilizing endogenous sources of protein (muscle) to meet amino acid needs. This can occur with an unbalanced diet

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or in a pet who is experiencing disease-­ associated cachexia. Cachexia is a complex metabolic syndrome that results in excessive loss of muscle and fat stores. It is important to remember that for some disease entities, like osteoarthritis (OA) and obesity, identifying the clinical signs can be challenging for very different reasons. Clinical signs of OA are often not obvious upon examination, particularly early in the disease process. Although signs of overweight/obesity are readily apparent, they are frequently overlooked or dismissed as inconsequential. Owners may attribute many signs of OA to normal aging, and as a result, fail to report them unless prompted. Recognizing the signs in cats can be much more difficult. Cats often suffer in silence and the healthcare team must rely upon the owner’s evaluation and thorough history to ascertain potential signs and symptoms. 17.1.1.2  Diet-­Related Components

There are multiple components to the diet component of the assessment. Beyond the name of the diet, identify what type of diet the pet is eating. Commercial diet types include kibble, canned, fresh, and raw (fresh, frozen, freeze-­dried, raw coated). Homemade diets can include cooked, and raw. Additionally, discover if the diet has any unconventional components like vegetarian, vegan, meat only, meat and bone, or human scraps from the table. Understanding how much the pet is being fed and how the diet is measured (scale, measuring cup, another tool, or not measured – free-­fed). Finally, inquire about incomplete and balanced sources of food, including treats, dietary supplements, or medications. No more than 10% of daily energy requirements should come from sources that are not complete and balanced. 17.1.1.3  Feeding Management

Factors such as the location of food and water dishes may play a role for pets who are experiencing pain. Difficulty getting to the dishes (stairs or other barriers) or positional

17.1 ­Nutrition – The 5th Vital Assessmen

concerns (neck pain making it difficult to bend) when they try to eat or drink may influence the pet’s ability to be properly nourished. Additionally, pets with inadequate or inappropriate housing may have additional stressors or influence the level of pain they need to manage (Kirk 2011).

17.1.2  Nutrition Plan After a nutrition assessment, a plan must be made for each individual animal to meet the pet’s life stage, and physiological needs to ensure it will properly address the pet’s needs (Kirk 2011). A nutrition plan should include (i) the energy requirements for the pet; (ii) a diet recommendation; (iii) a diet transition plan; (iv) a maintenance feeding plan; (v) supplements including specific recommendations (brand name and dose), administration dose, and frequency; and (vi) treat recommendations, including the amount to be fed. For pets on weight management programs, the addition of a chart where weights are listed may help pet parents visualize their pet’s progress. These charts are beneficial for growth, to support maintaining an ideal weight, or in weight loss to show a progression of loss to the goal weight.

17.1.3  Complete and Balanced Nutrition The phrase complete and balanced nutrition can have a broad definition depending on your nutritional theory. Humans attempt to have a nutritional profile that is balanced over a long period of time versus the pet industry, where diets are formulated to specifically meet a pet’s short-­term or daily nutritional needs. Regardless, a complete and balanced diet includes macronutrients, and micronutrients in balanced amounts for that pet’s species and life stage, along with providing adequate energy requirements. Energy requirements are coming from the nutrients provided; therefore, if excessive or insufficient energy is supplied to the pet, the pet will be in a state of imbalance or malnourishment.

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Noncommercial diets, including both cooked and raw homemade diets, are at a higher risk of providing unbalanced nutrition. A  2017 study by Perdinelli et al. evaluated 106 homemade diet recipes (80 canine, 24 feline, and 2 diets for both species) for nutritional adequacy. Almost half of the recipes (48%) had no precise listing of ingredients and quantities; all the diets had at least one nutrient below FEDIAF recommendations, with the most commonly deficient nutrients being iron, vitamin E, zinc, calcium, copper, choline, riboflavin, thiamine, and cobalamin (B12) (Pedrinelli et  al.  2017). Diets that are vegetarian or vegan may be difficult to properly formulate and produce for pets in a complete and balanced manner, particularly for cats (Dodd et al. 2021). Issues for these diets include the provision of balanced amino acids, fatty acids (arachidonic acid), and some essential nutrients for growth such as omega-­3 fatty acid DHA (Dodd et al. 2021). Complete and balanced nutrition is important for the prevention of malnutrition, a state of nutritional imbalance in energy provisions. Malnutrition is not only when there is nutrition restriction, as may be observed in a starving pet; it can additionally occur when a pet is provided with excess nutrients and is in an overweight or obese state (Molina et  al.  2018). Diets that are identified as complete and balanced should include an AAFCO Nutritional Adequacy Statement on the packaging of the diet. The Association of American Feed Control Officials (AAFCO) and the National Research Council (NRC) have created guidelines for nutritional adequacy statements for commercial pet food (Burdett et al. 2018). The Nutritional Adequacy statement should include how the food was determined to be complete and balanced (formulation, AAFCO feeding trial), and the life stage the diet was formulated for (Burdett et al. 2018). Diets may be listed as “intermittent and supplemental feeding” which would indicate this diet does not meet nutritional adequacy guidelines, as should be used as a supplemental diet for short-­term use or as a topper providing no more than 10% of calories.

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17.1.4  Obesity’s Role in Inflammation and Pain Nutrition can have a huge impact and should be considered an integral part of a pain management protocol. This is especially true when managing or preventing specific painful conditions. Obesity can be defined as an increase in fat tissue mass sufficient to contribute to disease. Dogs and cats weighing 10–19% more than the optimal weight of their breed are considered overweight; those weighing 20% or more above the optimum weight are considered obese (Burns and Towell  2011). Obesity has been linked with several disease conditions as well as with a reduced lifespan, with pets in this state experiencing constant low-­grade inflammation. A combination of excessive caloric intake, decreased physical activity, gut dysbiosis, and genetic susceptibility are associated with most cases of obesity, and the primary treatment for obesity is reduced caloric intake and increased physical activity. Obesity is one of the leading preventable causes of illness/death. With the dramatic rise in pet obesity over the past several decades, weight management and obesity prevention should be among the top health issues that healthcare team members discuss with every client. Pet obesity has reached epidemic proportions in the USA and other industrialized countries, which parallels the epidemic in the human population (Burns 2013). According to the Association for Pet Obesity Prevention (APOP), obesity has increased in both dogs and cats. Between 2010 and 2018, it was estimated that the percentage of pets diagnosed as either overweight or obese increased from 43% to 56% in dogs and from 53% to 60% in cats. The State of U.S. Pet Obesity  2022: Summary of Findings saw an increase in dogs and cats to 59% and 61%, respectively. When pet owners of over conditioned pets were asked if their “pet was obese or overweight,” 32% of pet owners classified these pets as having normal or ideal body condition. While 67% of pet owners surveyed said

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they “have not felt embarrassment or uncomfortable after being told their pet needed to lose weight,” 23% of dog owners and 29% of cat owners stated that “their pet did not lose weight despite their best efforts” (Association for Pet Obesity Prevention 2022). The veterinary profession can assume that a significant portion of arthritic dogs and cats will be overweight/obese and vice versa. Managing these comorbid conditions presents a variety of challenges for the healthcare team. Thus, owners of pets at risk for obesity and associated conditions like OA should be educated on the importance of lifelong weight management and should be reminded that overweight puppies or kittens will become overweight adult dogs and cats. Veterinary healthcare teams are in the unique position of being able to counsel owners on more appropriate responses early in a pet’s life. Owners should be encouraged to respond with play activities or praise rather than food rewards. It is imperative that the veterinary healthcare team members, especially the veterinary technician, communicate with the client regarding the disease of obesity, the potential risks associated with obesity, and the relationship between the pet being overweight and increased signs/symptoms of OA (Figures 17.1 and 17.2).

17.1.5  Key Nutritional Factors As discussed, the most important part of nutrition is ensuring that it provides complete and balanced nutrition for the pet. When managing a pet’s life stage or disease state, specific nutrients have been identified as being key factors influencing the health of the pet. These key nutritional factors include recommendations in the type and volume of the nutrient in a diet to aid in improving the health status of the pet. Water, macronutrients (protein, fat, and carbohydrates), micronutrients (vitamins, and minerals), and other nutrients such as polyunsaturated fatty acids can improve the pet’s health.

17.1 ­Nutrition – The 5th Vital Assessmen

Figure 17.1  Body condition score (BCS) descriptors for dogs in a five-­point system. BCS 1. Very thin: The ribs are easily palpable with no fat cover. The tailbase has a prominent raised bony structure with no tissue between the skin and bone. The bony prominences are easily felt with no overlying fat. Dogs over 6 months of age have a severe abdominal tuck when viewed from the side and an accentuated hourglass shape when viewed from above. BCS 2. Underweight: The ribs are easily palpable with minimal fat cover. The tailbase has a raised bony structure with little tissue between the skin and bone. The bony prominences are easily felt with minimal overlying fat. Dogs over 6 months of age have an abdominal tuck when viewed from the side and a marked hourglass shape when viewed from above. BCS 3. Ideal: The ribs are palpable with a slight fat cover. The tailbase has a smooth contour or some thickening. The bony structures are palpable under a thin layer of fat between the skin and bone. The bony prominences are easily felt under minimal amounts of overlying fat. Dogs over 6 months of age have a slight abdominal tuck when viewed from the side and a well-­proportioned lumbar waist when viewed from above. BCS 4. Overweight: The ribs are difficult to feel with moderate fat cover. The tailbase has some thickening with moderate amounts of tissue between the skin and bone. The bony structures can still be palpated. The bony prominences are covered by a moderate layer of fat. Dogs over 6 months of age have little or no abdominal tuck or waist when viewed from the side. The back is slightly broadened when viewed from above. BCS 5. Obese: The ribs are very difficult to feel under a thick fat cover. The tailbase appears thickened and is difficult to feel under a prominent layer of fat. The bony prominences are covered by a moderate to thick layer of fat. Dogs over 6 months of age have a pendulous ventral bulge and no waist when viewed from the side due to extensive fat deposits. The back is markedly broadened when viewed from above. A trough may form when epaxial areas bulge dorsally. Source: Mark Morris Institute.

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Figure 17.2  BCS descriptors for cats in a five-­point system. BCS 1. Very thin: The ribs are easily palpable with no fat cover. The bony prominences are easily felt with no overlying fat. Cats over 6 months of age have a severe abdominal tuck when viewed from the side and an accentuated hourglass shape when viewed from above. BCS 2. Underweight: The ribs are easily palpable with minimal fat cover. The bony prominences are easily felt with minimal overlying fat. Cats over 6 months of age have an abdominal tuck when viewed from the side and a marked hourglass shape when viewed from above. BCS 3. Ideal: The ribs are palpable with a slight fat cover. The bony prominences are easily felt under a slight amount of overlying fat. Cats over 6 months of age have an abdominal tuck when viewed from the side and a well-­proportioned lumbar waist when viewed from above. BCS 4. Overweight: The ribs are difficult to feel with moderate fat cover. The bony structures can still be palpated. The bony prominences are covered by a moderate layer of fat. Cats over 6 months of age have little or no abdominal tuck or waist when viewed from the side. The back is slightly broadened when viewed from above. A moderate abdominal fat pad is present. BCS 5. Obese: The ribs are very difficult to feel under a thick fat cover. The bony prominences are covered by a moderate to thick layer of fat. Cats over 6 months of age have a pendulous ventral bulge and no waist when viewed from the side due to extensive fat deposits. The back is markedly broadened when viewed from above. A marked abdominal fat pad is present. Fat deposits may be found on the limbs and face. Source: Mark Morris Institute.

17.1.6  Macronutrients and Micronutrients When managing patients experiencing pain, the balance of macronutrients includes an assessment of many factors that should be gathered when taking a history. Many of these

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pets will require a sufficient provision of protein to meet demands and decrease the risk of metabolization of endogenous sources. One macronutrient that may be currently undervalued when considering diet choices is fiber. As

17.2 ­Microbiota Healt

we consider gut health to support host health, ensuring that a source of fermentable fiber is included in the diet ensures commensal microbe function, metabolism of  short-­chain fatty acids (SCFA) to aid in decreasing inflammation, and supporting neurological functions (Zhang et al. 2017). Micronutrients play a crucial role as they support metabolic functions, the production of tissue, and support neurological functions. Pets on unconventional diets should have a thorough nutritional evaluation completed and assessed to ensure there is not an ­imbalance in micronutrient provision.

17.1.7 Antioxidants Antioxidants are beneficial in reducing free radicals by preserving the structural integrity and function of biological molecules in cells (Hand et al. 2011). Additionally, antioxidants will affect the gut microbiome by decreasing relative oxidative stress. With 70% of immune cells located in the intestines, lymphocyte accumulation can initiate a change in ­microbiota composition. Gut inflammation can affect the gut-­brain axis and corresponding neurological functions (Perini et al. 2020). Natural antioxidants include vitamins E, C, β-­carotene, and selenium (Hand et al. 2011).

17.1.8  Nutrient-­Focused Diets Therapeutic commercial diets are formulated to aid in nutritionally supporting specific disease states to nutritionally influence and benefit the pet. Anti-­inflammatory diets, such as those for joint support, include increased omega-­3 fatty acids (Panickar and Jewell 2018). Additionally, the provision of less inflammatory ingredients like beef, the inclusion of flavonoids, turmeric, curcumin, zinc, prebiotics, and the probiotics like Saccharomyces boulardii provide immune support and decrease inflammation (Panickar and Jewell 2018; Zhang et al. 2016). Anti-­angiogenic diets are focused on reducing the ability of a tumor to develop and

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reducing the proliferation of blood vessels to support its growth. These diets include a reduction of simple carbohydrates, which are the preferred source of nutrients for neoplastic cells (Perini et  al.  2020). Additionally, these diets usually include increased antioxidant and anti-­inflammatory support. Adaptogenic diets utilize plants or mushrooms to decrease the poor effects of stress and anxiety to promote and restore normal physiological function. More research is needed in these diet-­focused areas in dogs and cats.

17.2  ­Microbiota Health 17.2.1  Prebiotics Prebiotics are nutrients that feed microbiota that result in a positive shift for the host. Prebiotics are indigestible by the host with the nutrient undergoing microbial fermentation by commensal bacteria resulting in beneficial metabolites such as SCFA. Oligosaccharides are one of the most studied forms of prebiotic fibers coming from, but not limited to, artichokes, onions, bananas, wheat bran, chicory, broccoli, and blueberries (Perini et  al.  2020; Jory  2017). These fibers are particularly ­important as the resulting production of SCFAs improves barrier function, decreasing immune responses and corresponding inflammation.

17.2.2  Probiotics Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” (Hill et  al.  2014; Salminen et  al.  2021). Probiotics have certain characteristics (Reid 2016): ●●

●●

They must be alive and viable at the time of consumption. They must be able to survive the different environments through the gastrointestinal tract including gastric acid and be able to resist digestion by intestinal enzymes.

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●●

The bacteria being used should be considered safe and nonpathogenic. They must promote a normal and balanced microbiome by either enhancing the commensal bacteria or suppressing the growth or colonization of pathogenic bacteria.

Probiotics protect the host from pathogenic bacteria through competition exclusion which includes the bacteria-­to-­bacteria competition for available nutrients, space, or eliciting antimicrobial effects (Reid 2016). Some probiotics produce beneficial metabolites to improve physiological functions and host health. Many probiotics are in the form of bacteria, though fungi are being utilized as they lack direct competition with beneficial gut bacteria. Saccharomyces boulardii, is a well-­studied yeast that appears to have intestinal anti-­ inflammatory effects, relieving visceral pain (Pothoulakis 2009). The concern with probiotics in North America is the lack of regulations in pets. If the probiotic label does not indicate any health claims, the probiotics are considered to be a nutraceutical or supplement and therefore do not have the same regulations placed on them as pharmaceuticals with regards to viability studies, dosing, and expiry of products. Concerns with products that are not regulated include inconsistency in the content versus what is listed on the label, use of pathogenic or antimicrobial resistant bacteria, inappropriate or untested dosage, ineffective product, or release of harmful metabolites (Siddiqui and Moghadasian 2020).

17.2.3  Fecal Microbial Transplant (FMT) Fecal microbial transplant (FMT) material is quickly becoming the bacterial product of choice for treating gut dysbiosis. FMT material is screened feces that is collected from a healthy donor. Screening includes meeting basic signalment criteria, being free of any general health concerns, metabolic diseases, and parasitic infestation. Fecal microbial

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profile should be completed to ensure that normal, beneficial bacteria are being provided within a normal reference range (Ganz et al. 2022). The FMT material can then be provided to a patient of the same species, either via enema or orally to provide species-­specific microbes to the patient. In some instances, this may also provide metabolites like SCFA, and other beneficial components to the patient. Enema procedures are showing quick, and identifiable improvements in patient symptoms post receiving FMT material from healthy donors. Research has been utilizing this type of procedure in germ-­free mice to identify gut microbes’ role in disease states (Ademe 2020). Oral application of FMT material requires that the product be placed in an enteric-­coated capsule to ensure that the live microbes are protected from the antimicrobial actions of the upper gastrointestinal tract. FMT may have therapeutic effects through several mechanisms, ­including direct competition with pathogenic bacteria, protecting and improving the intestinal barrier, correction of bile acid dysmetabolism, and stimulation of the immune system. These mechanisms may aid in improving visceral and chronic pain (Ademe 2020).

17.2.4  Postbiotics A postbiotic is defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as “preparation of inanimate microorganisms and/or their components that confers a health benefit on the host” (Salminen et al. 2021). In a sense, a postbiotic may be similar to microbial metabolites, though it is produced as a food form. Postbiotics are provided orally to aid the host where there are insufficient microbial metabolites produced to create a similar effect. In cases of dysbiosis, postbiotics can be added to the diet until beneficial bacteria can be re-­established and function normally (Ademe  2020; Żółkiewicz et al. 2020). Postbiotics are not the same as synbiotics, which include a probiotic and a prebiotic provided together.

17.3 ­Cannabinoid Medicin

17.3  ­Cannabinoid Medicine 17.3.1  History of Cannabis The medicinal and spiritual use of cannabis can be traced back over 10 000 years to central and Southeast Asia (Crouq  2020; Rech and Narouze 2021). It is hypothesized that hemp and cannabis plants were initially used for their fiber in the production of nets, ropes, and clothing, while the hemp seed was used in food and oils. Dating back to the twelfth ­century, it was customary to use cannabis in

ayurvedic medicine to treat “pain, inflammation, and anxiety,” as well as to “improve sleep, appetite, and relaxation.” This medicinal herb, known as vijaya in Sanskrit, migrated to Europe and around the world, becoming prevalent in both human and veterinary medicine (Frankhauser  2002; Russo  2021). The first hemp crop to be cultivated in North America was in Acadia (known today as Nova Scotia), by a French botanist Louis Hebert in 1606 (McGillvray  2017). In 1839, William Brooke O’Shaughnessy, an Irish physician working in Calcutta, published his clinical observations,

Table 17.1  Section abbreviations. 2-­AG – 2-­arachidonoylglycerol

FABPs – fatty acid binding proteins

AEA – anandamide

GABA – gamma aminobutyric acid

AA – arachidonic acid

GlyR – glycine receptor

ALP – alkaline phosphatase

GPCR – G-­protein coupled receptor

AMP – adenosine 5-­monophosphate

HRE – harm reduction education

Akt – serine/threonine-­specific protein kinase

IL-­6/IL-­12 – interleukin 6/interleukin 12

CB1 – cannabinoid receptor 1

LD 50 – median lethal dose

CB2 – cannabinoid receptor 2

LOX – lipoxygenase

CBCA – cannabichromenic acid

MCT – medium chain triglycerides

CBC – cannabichromene

MGL – monoacylglycerol lipase

CBDA – cannabidiolic acid

NMDA – N-­methyl-­d-­aspartate

CBD – cannabidiol

OPM1 – opioid receptor (M – mu, D – delta, K – kappa)

CBDV – cannabidivarin

PGE2 – prostaglandin E2

CBGA – cannabigerol acid

PK – pharmacokinetic

CBG – cannabigerol

PNS – peripheral nervous system

CBN – cannabinol

PPARα – peroxisome proliferator-­activated receptor alpha

CNR1 – cannabinoids receptor 1 gene

PUFAs – polyunsaturated fatty acids

CNR2 – cannabinoid receptor 2 gene

ROS – reactive oxygen species

CNS – central nervous system

THCA – tetrahydrocannabinolic acid

COA – certificate of analysis

THC – delta-­9-­tetrahydrocannabinol

COX 1 and COX 2-­cyclooxygenase 1 and 2

THCV – tetrahydrocannabivarin

DRG – dorsal root ganglion

TNF-­α – tumor necrosis factor alpha

EA – electroacupuncture

TRPA1 – transient receptor potential ankyrin type-­1

eCBome – endocannabinoidome

TRPV1 – transient receptor potential vanilloid type 1

ECS – endocannabinoid system

RPM8 – transient receptor potential melastatin 8

FAAH – fatty acid amide hydrolase

VCPR – veterinary-­client-­patient-­relationship

VHP – veterinary health products

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discussing the narcotic-­like effects of cannabis through experimentation on dogs, cats, fish, swine, and vultures. O’Shaughnessy established human applications for cannabis in the treatment of rheumatism, cholera convulsions, and tetanus (McGillvray 2017; Russo 2021). It is believed that from O’Shaughnessy’s work, cannabis became a popular medicinal treatment for a wide range of human and veterinary conditions throughout Europe and North America. In veterinary textbooks dating back to the 1900s, there is extensive literature documenting the clinical application of cannabis in a wide variety of species. The evolution of these applications led to the discovery of cannabinoid molecular structures, physiological systems, and contributed to significant scientific breakthroughs. One of the earlier documented discoveries was that of cannabinol (CBN) in the 1930s, with its chemical synthesis being isolated by Roger Adams and Alexander Todd in 1940 (Pertwee  2006). The stereochemistry and molecular isolation of the well-­known “major” cannabinoids cannabidiol (CBD) and delta-­9-­tetrahydrocannabinol (THC) by Israeli chemist Dr. Raphael Mechoulam took place in 1963 and 1964, respectively (Pertwee  2006; McGillvray 2017). Cannabis research continued throughout the 1960s but sharply declined in 1970  when the United States government classified cannabis as a Schedule 1 drug under the Controlled Substances Act. This classification limited further research into the plant because it was considered to have no acceptable medical use and a high abuse potential. The early discovery and initial synthesis of cannabinoids was the catalyst for future research leading to the identification of the cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) in the late 1980s and early 1990s, both encoded by their associated genes (CNR1 and CNR2), respectively (Murphy et  al.  2021). Further research identified these

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endogenous receptors as G-­protein coupled receptors (GPCR) and explored their distribution throughout the central and peripheral nervous systems (PNS) (Silver  2021). Two researchers at the Saint Louis University School of Medicine, Allyn Howlett and William Devane, identified a sophisticated, physiological system present in all vertebrates while investigating the mechanism of action of THC. In 1988, this intricate, cell-­signaling ­regulatory system was coined the endocannabinoid system (ECS) (Pertwee  2006; McGillvray 2017).

17.3.2  Cannabis Potential in Veterinary Medicine Documented human research on the medicinal and therapeutic benefits of cannabis dates to before the turn of the century. This research has proven that vertebrates, and some invertebrates, experience physiological influences imposed by the relationships between endocannabinoid ligands, biological enzymes, cannabinoid, and non-­cannabinoid receptors. There is significant scientific interest in the potential uses of cannabis in veterinary medicine, much of it having been initially extrapolated from human studies. The veterinary community has observed improved patient mobility through analgesic and anti-­ inflammatory properties, reduced anxiety, increased appetite, and enhanced epileptic seizure control. Cannabinoids and cannabinoid receptor activation can modulate dermatological conditions and metabolic diseases including obesity, and can improve the regulation of type 2 diabetes. Major and minor cannabinoids have demonstrated cardiovascular and pulmonary effects, anxiolytic, antioxidant, and neuroprotective properties as well as inhibition of tumor growth and tumor cell apoptosis (Guzmán et al. 2016; Hartsel 2019; Hinz and Ramer 2019; Banerjee et  al.  2020; Wakshlag et al. 2020; Williamson et al. 2021).

17.4 ­The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome

17.4  ­The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome) It wasn’t until almost three decades after the identification of the major plant cannabinoids that the ECS was discovered. The ECS is a system of balance and chemical feedback that has modulatory effects including but not limited to the nervous, immune, cardiovascular, and reproductive systems. This complex system contributes to inter and intra-­cellular communication while playing a regulatory role within the central and PNS to maintain homeostasis. The diversity of the ECS regulatory functions encompass one’s emotional responses, energy balance, metabolism, appetite, sleep management, anxiety, inflammation, and immune system homeostasis (Di Marzo  2020; Mosley et  al.  2021; Payten et  al.  2021; Russo  2021; Silver  2021). This classic system consists of endocannabinoids (endogenous ligands), anabolic/­catabolic enzymes, and the receptors (CB1 and CB2) to which cannabinoids bind. Over the last few years, an extension of the ECS known as the endocannabinoidome (eCBome), has been a noteworthy subject of scientific research. The eCBome plays an impactful role in a significant number of physiological functions and disease processes. This expanded system incorporates over 20  non-­ ECS receptors and 20  non-­ECS ligands that interact with endogenous and exogenous cannabinoids (Di Marzo and Piscitelli  2015; Anderson et  al.  2019). The eCBome has an affinity for receptors we are more familiar within veterinary medicine, including opioid, serotonin, dopamine, TRPVs (transient receptor potential vanilloid types), and numerous GPCRs (Di Marzo 2020; Copas et al. 2021; Rech and Narouze 2021; Mosley et  al.  2021). In humans and animals there is growing evidence to support the involvement of the eCBome in several disorders including anxiety, depression, metabolic conditions, gastrointestinal disease, pain, and cancer (McCabe and Cital 2021;

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Guzmán et  al.  2016; Hartsel  2019; Lian et  al. 2022; Banerjee et al. 2020; Wakshlag et al. 2020; Lian et al. 2022). Having a well-­balanced ECS and eCBome contributes to uniformity among other physiological systems and the maintenance of homeostasis (Pertwee 2001).

17.4.1  Primary Cannabinoid Receptors Cannabinoid receptors CB1 and CB2 are GPCRs activated by three major groups of ligands: endocannabinoids, exogenous phytocannabinoids (plant-­derived cannabinoids), and synthetic (manufactured) cannabinoids. CB1 receptors have high-­density expression in the nervous system with locations on presynaptic neurons, DRG (dorsal root ganglion), and superficial laminae of the spinal cord, as well as extensive regions of the brain, including the amygdala, hippocampus, cerebellum, and cerebral cortex. It is the density of this neuronal expression, particularly in the hindbrain structures of the canine species, that mediates the psychoactivity of some cannabinoid molecules, particularly that of THC (Herkenham et  al. 1990; Silver  2019; Brutlag  2021). Apart from the CNS, PNS expression of the CB1 receptor is observed in endocrine, immune, reproductive, cardiovascular, and digestive systems (Pertwee 2001; Russo  2020; Copas et  al.  2021; Rech and Narouze 2021). The CB2 receptor is mainly located on immune cells found in the spleen, thymus, gastrointestinal tract, and lymph nodes and is highly inducible, increasing 100x after tissue injury and at sites of inflammation. This receptor has central locations on glial and endothelial cells and in the DRG and dorsal horn of the spinal cord, and peripherally on postsynaptic neurons (Mosley et al. 2021). Healthy, uninjured tissues contain low numbers of CB2 receptors, in contrast, inflamed or injured tissues have an increased number of CB2 receptors (Dhopeshwarkar and Mackie  2014; Mosley et  al.  2021). The inducibility of this receptor contributes to the

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role it can play in acute, chronic, neuropathic, and inflammatory pain (Copas et  al.  2021; Rech and Narouze 2021). In summary, CB1 is ­primarily a neuro-­modulatory receptor and CB2 is referred to as a peripheral immuno-­ modulatory receptor.

17.4.2  Endocannabinoids All chemical substances that elicit a physiological response at the CB1 and CB2 are considered cannabinoids. Endocannabinoids are endogenous, lipid-­based neurotransmitters naturally found within the body. These lipophilic molecules are produced on-­demand through depolarization or activation of specific GPCRs and elicit their action on the presynaptic cannabinoid receptor. Polyunsaturated fatty acids (PUFA) are key components in the synthesis of the body’s endogenous cannabinoids, with evidence that omega 3 and omega 6 fatty acids play a role in endocannabinoid signaling, deficiencies, and system tonicity (Lafourcade et  al.  2011; Freitas et  al. 2017; Watson et al. 2019). Five endocannabinoids have been identified, with the most researched involving anandamide (AEA) and 2-­arachidonoylglycerol (2-­ AG). These endogenous ligands participate in orthosteric binding at the cannabinoid receptor site to elicit physiological responses (Lu and Makie  2015; Copas et  al.  2021; Pete and Narouze 2021). The number of endocannabinoids present in one’s body is known as their “endocannabinoid tone.” With the on-­demand production and short half-­life of these molecules, there is not a numerical digit given as a “normal” level of endocannabinoids, as each individual’s tonicity varies (Hartsel  2019). Trauma, inflammatory processes, and subsequent cell depolarization prompt endocannabinoid production. The reduction in one’s endocannabinoid tone is the catalyst for a variety of chronic and inflammatory disease processes documented in humans (Vuckovic et  al.  2018; Banerjee et  al.  2020). Factors that have been noted to influence an individual’s tonicity are the quantity of

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endocannabinoids and their associated enzymes, extent of receptor distribution, role of genetic receptor variants (Akt, CB1, CB2), and the molecular composition and dosing of the chosen cannabis product (Silver 2019). Anandamide, also known as N-­arachidonoyl ethanolamine, is a partial agonist on the CB1 and CB2 receptors, a full agonist on TRPV1 (transient receptor potential vanilloid type 1) and produces a similar physiological response to that of THC on the CB1 (Lu and Makie 2015; Copas et al. 2021; Pete and Narouze 2021). This endocannabinoid has demonstrated anti-­ inflammatory and analgesic properties through modulation of TRPV1 receptor activation (Pete and Narouze 2021), induction of CB1 and CB2 receptors modulating nociception and inflammation, as well as metabolic regulatory processes attributed to PPARα (peroxisome proliferator-­activated receptor α) binding (Lu and Makie 2015; Di Marzo and Silvestri 2019; Pete and Narouze 2021). 2-­AG is a full agonist at both CB1 and CB2 receptors and is postulated to play a more significant role than anandamide in antinociception due to its increased nervous system tissue concentration and distribution. 2-­AGs prominent expression in the brain and essential role in the retrograde signaling and downregulation of both GABA and glutamate neurotransmitters, contributes to the endocannabinoids neuromodulatory recognition (Justinová et al. 2011; Di Marzo 2020; Pete and Narouze 2021). Modulation of receptor function and endocannabinoid tone is affected by endocannabinoid transporters. To transfer endocannabinoids through aqueous mediums like cytoplasm, these lipophilic molecules require a method of transportation. Fatty acid binding proteins (FABPs) are essential components in the uptake of PUFAs and are known transporters of endocannabinoids, delivering them to their specific catabolic enzyme (Deutsch  2016; Zhang et al. 2018; Hartsel 2019). Restriction in FABP availability or PUFAs such as omega 3s, can contribute to a reduction in endocannabinoid transfer and subsequent metabolism through which arachidonic acid is

17.4 ­The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome

a by-­product, contributing to inflammation (Hartsel  2019; Banerjee et  al.  2020; Di Marzo 2020). A 2023 study in mice receiving a diet rich in soybean oil revealed an increase in irritable bowel disease (IBD) symptoms, including ulcerative colitis. It was hypothesized that the increase in the omega 6 fatty acid, linoleic acid, played a role in the reduction of the body’s endogenous cannabinoids and their anti-­inflammatory properties (Deol et al. 2023). The main metabolizing enzyme of AEA is fatty acid amide hydrolase (FAAH), which hydrolyzes the endocannabinoids into ­arachidonic acid (AA) and ethanolamine. Monoacylglycerol lipase (MGL) hydrolyzes 2-­AG into AA and glycerol. The breakdown of 2-­AG is considered a substantial source of ­arachidonic acid, and therefore the inhibition of  its metabolizing enzyme can decrease prostaglandin-­mediated inflammation. It is well documented that arachidonic acid is the precursor to prostaglandins and other eicosanoids. Both endocannabinoids AEA and 2-­AG, including their catabolic enzymes, have been documented to play a key role in the inflammatory (eicosanoid) pathways (Mosley et al. 2021).

17.4.3  Retrograde Signaling The ECS and corresponding receptors participate in a one-­of-­a-­kind retrograde transmission operation. After an excitatory or inhibitory neurotransmitter has been released from vesicles within the presynaptic neuron, they travel across the synaptic cleft, depolarizing a postsynaptic neuron. Activation of the postsynaptic neuron contributes to the on-­demand synthesis and release of endogenous cannabinoids. The endocannabinoids then proceed to move in a retrograde manner (backward) across the synapse, binding to presynaptic neurons heavily populated with CB1 receptors. Retrograde activation of the presynaptic ­cannabinoid receptors allows for neuronal potentiation or inhibition of neurotransmitters, demonstrating how the ECS contributes to the regulation and homeostasis of the nervous system (Lu and Makie  2015;

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Andre et  al.  2020; Banerjee et  al.  2020; Williamson et al. 2021).

17.4.4  Exogenous Cannabinoids Clinical modulation of the ECS can be achieved using exogenous molecules and external modalities. The role of exogenous cannabinoids is to influence the body’s concentrations of endogenous cannabinoids and corresponding receptors, eliciting a physiological response. Natural or synthetic external molecules antagonize the body’s ECS receptors. These molecules are chemically manufactured in a laboratory, synthetic cannabinoids, or are extracted from the glandular trichomes of hemp or cannabis plants. Plant-­based cannabinoids are known as phytocannabinoids, “phyto” coming from the Greek word phyton meaning plant. There have been well over 100 phytocannabinoids identified in the Cannabis sativa plant. A significant portion of them are known analogs of the two major cannabinoids (THC and CBD) and six minor cannabinoids, including CBC (cannabichromene), CBG (cannabigerol), and CBN (cannabinol) (Hartsel  2019; Copas et  al.  2021; Roychoudhury et al. 2021). Modern medicine has allowed for the identification of principal receptors and abnormal gene expressions within disease processes. These discoveries then allow for laboratory designed chemicals capable of high-­affinity receptor binding in an attempt to treat a disease or symptom within a disease process. There are medicinal benefits to the creation of synthetic cannabinoids; however, there is an inherent increased risk of adverse events and intoxications due to the increased potency over phytocannabinoids (Archana et al. 2021). Most prescription cannabis health products in human medicine have limited use in the veterinary world due to their adverse side effects. Examples of such products are Sativex® (­nabiximols), an approximately 1.1 : 1 THC: CBD peppermint mouth spray approved for multiple sclerosis (MS)-­related muscle spasticity (Russo et al. 2015), and Cesamet® (nabilone), a synthetic cannabinoid (THC) approved

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for  nausea and vomiting secondary to ­chemotherapy treatment (US Food and Drug Administration 2006).

17.4.5  Major Cannabinoids THC is one of the two well-­known major cannabinoids being researched in human and veterinary medicine. THC is the predominant molecule responsible for the intoxicating effects of cannabis, exerting orthosteric binding and partial agonistic expression at both the CB1 and CB2 receptors (Shahbazi et  al.  2020). THC has notable medicinal and therapeutic properties, including analgesia via various receptor activations and altered perception of conscious pain. THC contributes to inflammatory modulation through non arachidonic acid pathways, and it possesses antiemetic and anticonvulsant properties. Less familiar benefits include reducing ocular pressures, neuroprotective effects, and bronchodilation (Evans 1991; Azuara-­Blanco et  al.  2006; Benjaminov et  al.  2013; Kendall and Yudowski 2016; Couch et al. 2017; Andre et  al.  2020; Axelrod et  al.  2000; Banerjee et al. 2020; Giuliano et al. 2021). The second of the well-­known major cannabinoids is cannabidiol. CBD is a diverse and dynamic molecule that acts as an endocannabinoid modulator by influencing the behavior of other endocannabinoids. An example of this is CBD inhibition of the reuptake of AEA, allowing for prolonged physiological influence within the body, and the molecule’s allosteric binding to the CB1 receptor modulating the physiological effects of THC (Deutsch 2016). Much of the previous literature simplified CBD as a partial agonist at CB2 and an antagonist at CB1. However, the complexity of this cannabinoid has led to the consideration of over 65 target receptors including glycine, serotonin (5-­HT), opioid, peroxisome proliferator-­activated receptor (PPAR), and multiple G-­coupled receptors, GPR18 and GPR55 (Bazelot et  al.  2015; Banerjee et  al.  2020). Medicinal and therapeutic applications of CBD include analgesia,

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anti-­inflammatory, anxiolytic, antiemetic and neuroprotective properties, as well as inhibition of tumor growth and anticonvulsant effects (Perucca  2017; Hartsel  2019; Andre et  al.  2020; Banerjee et  al.  2020; Hinz and Ramer 2019).

17.4.6  Minor Cannabinoids Although the most researched and familiar phytocannabinoids are CBD and THC, there are over 100 of these molecules being investigated for their medicinal attributes (Copas et  al.  2021; Roychoudhury et  al.  2021; de Lorimier et  al.  2021). Cannabigerol acid (CBGA) is the acidic form of CBG and is the molecular grandfather for the majority of phytocannabinoids, participating in the synthesis of CBD and THC. Cannabigerol (CBG) is thought to be a weak partial agonist at CB1 and CB2 and inhibits the reuptake of AEA and gamma aminobutyric acid (GABA) contributing to muscle relaxation (Navarro et al. 2018; Banerjee et al. 2020). CBG has been shown to have strong analgesic, anti-­inflammatory, and antidepressant properties due to its serotonin and α2-­adrenoreceptor activity, as well as activation of PPARγ. Suppression of TRPV1 and transient receptor potential melastatin 8 (TRPM8) activity has led to research into the therapeutic potential of CBG in various cancers, autoimmune, and cardiovascular diseases (Banerjee et  al.  2020; Kogan et  al.  2021; Amstutz et al. 2022). The phytocannabinoid CBN (cannabinol) is a by-­product of THC degradation and primarily found in aged cannabis products. This molecule has been shown to have antibacterial attributes as well as anti-­inflammatory properties via various activities within transient receptor potential (TRP) cation channels and inhibition of the cyclooxygenase (COX) and lipoxygenase (LOX) pain pathways (Banerjee et  al.  2020; Gonçalves et  al.  2020; Clarke et al. 2021; Mosley et al. 2021). Cannabichromene (CBC) is a selective antagonist of the CB2 receptor possessing anti-­inflammatory properties via its binding with TRP channels of both

17.4 ­The Endocannabinoid System (ECS) and Endocannabinoidome (eCBome

TRPV1 and the ankyrin type-­1 receptor (TRPA1) (Udoh et al. 2019; Banerjee et al. 2020). CBDV (Cannabidivarin) and THCV (Tetrahydrocannabinolic Acid) are homologs of CBD and THC, respectively. These acidic cannabinoids are nonpsychotropic and possess anticonvulsant and antineoplastic properties (Chakravarti et  al.  2014; Moreno-­Sanz  2016; Rock et  al.  2016; Anderson et  al.  2019; Dariš et al. 2019; Banerjee et al. 2020) as well as anti-­ inflammatory effects demonstrated through COX-­2 inhibition (Takeda et al. 2008; Banerjee et al. 2020). A point of discussion that has transferred from human medicine is that of cannabinoid tolerance and the risk of reduction in physiological effects from chronic exposure. Repeated stimulation, particularly that of CB1, via endo or phytocannabinoid activation can result in receptor desensitization and incidents of tolerance (Maldonad  2002; González et  al.  2005). Investigating patient cannabinoid tolerance can be challenging, particularly in veterinary patients due to significant variabilities in time of onset, duration, and extensiveness of diminished physiological effects. Tolerance is usually only reserved for molecules that bind to the primary or orthosteric binding site of a receptor, as with THC. CBD and a majority of the other phytocannabinoids bind to what are called allosteric binding sites, making tolerance less likely.

17.4.7  Terpenoids and Flavonoids Hemp and THC-­containing-­cannabis plants are similar in that their leaves and flowers contain trichomes. Trichomes are glandular structures that contribute to the production of phytocannabinoids, terpenes, and flavonoids. Terpenes are naturally occurring hydrocarbon molecules found in plants and flowers. To date, approximately 50 000 phytochemicals have been identified, 200 of them within the Cannabis sativa plant (Christianson  2008; Gallily et  al.  2018; Banerjee et al. 2020). These molecules are commonly used in aromatic and essential oils and are known to have therapeutic benefits and

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contribute to the synergistic modulation of other cannabinoid molecules when used in ­conjunction (Russo  2011; Hughston and Conarton  2021). Some of the most prevalent ­terpenes are beta-­caryophyllene, linalool, limonene, and myrcene. Beta-­caryophyllene is the predominant terpene found in hemp/cannabis plants and has a peppery aroma. This terpene is also found in black pepper, hops, cloves, and cinnamon, and research has shown that it has medicinal properties such as analgesia, anti-­inflammatory, antioxidant, and gastroprotection (Klauke et al. 2014). Beta-­caryophyllene has been documented to be a potent agonist at the CB2 receptor, contributing to the terpenes’ anti-­inflammatory effects (Klauke et  al. 2014). The uniqueness of this terpenes’ receptor agonism allows it to be recognized by many as a cannabinoid (Hughston and Conarton  2021). Linalool is found in lavender, rosewood, sage, and thyme, and has anxiolytic, analgesic, anti-­ inflammatory, anticonvulsant, and sedative properties. Citrus fruit rinds contain high concentrations of limonene and have been documented to decrease depression, anxiety, and inflammation, and have demonstrated antineoplastic properties. This terpenes modulation of inflammation is through the reduction of prostaglandin E2 (PGE2) production (Yu et al. 2017). Myrcene has an earthy/fruity aroma and is found in hops, thyme, mangos and lemongrass. This terpenoid is bountiful in cannabis plants and is known for its analgesia, antioxidant, anti-­ inflammatory and muscle relaxation properties (Russo 2011; Hughston and Conarton 2021). An interesting attribute of myrcene is that its opioid-­like analgesia can be antagonized by naloxone, postulating biochemical interaction with opioid receptors (Hartsel 2019). Flavonoids are like terpenes in that they give plants and flowers their distinct color and aroma. Cannabis-­specific flavonoids are known as cannaflavins and are generally rich with antioxidants (Mosley et al. 2021; Hughston and Conarton 2021; Arboleda and Prosk 2021). Aside from being abundant in antioxidants, the over 20 documented cannaflavins also exhibit medicinal properties such as

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anti-­inflammatory, antiviral and neuroprotection. The anti-­inflammatory properties of flavonoids can be attributed to inhibition of inflammatory enzymes including prostaglandin E2 (PGE2) (Rea et al. 2019; Romagnolo and Selmin 2012; Silver et al. 2021). A study published in 2019 demonstrated therapeutic potential of cannaflavin B in animals with pancreatic cancer. The in vivo results demonstrated delayed metastatic tumor progression and increased survival times (Moreau et al. 2019).

17.4.8  Entourage Effect and Synergy A fascinating attribute of the cannabis plant is that the sum of all the molecular compounds work synergistically, producing a more enhanced physiological effect than that of a single molecule. The synergy between various phytocannabinoids and other molecular compounds from plants, and even conventional medications, is known as the entourage effect. The results of this synergy can lead to an increased therapeutic potential due to compounding molecular benefits while mitigating the adverse events that can be observed from administering increased concentrations of a single molecule (Russo  2019; Hughston and Conarton 2021).

17.5  ­Cannabinoid Role in Pain Management The ECS plays an essential role in all facets of the nociceptive pathway, involving itself in excitatory and inhibitory pathophysiological processes and signaling. Activation of CB1 or CB2 receptors via endo, phyto, or exogenous cannabinoids, or modulation of receptor catabolic enzymes, contribute to analgesic and anti-­inflammatory effects. Direct inhibition of COX1 and COX 2 receptors resulting in inflammatory reduction has been documented with THCA, CBDA, CBGA, and CBG. CBD can interfere with inflammatory cascades through activation of the TRP subfamilies (TRPV1, TRPV2, TRPA1, TRPM8). THC stimulates the

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lipoxygenase pathway and inhibits prostaglandin E2 synthesis, while CBD is known for its endocannabinoid modulation via reuptake inhibition. The ECS is an essential component in the anti-­inflammatory effects we depend on when implementing nonsteroidal anti-­ inflammatories (NSAIDs) in our veterinary patients (Mosley et al. 2021). Nociception, peripheral and central sensitization are influenced by oxidative stress. High levels of reactive oxygen species (ROS) are known to be noxious, potentially leading to protein, lipid, and DNA damage (Hendrix et  al.  2020). Endocannabinoids with antioxidant properties, such as CBD, THC, CBG, and CBN, can decrease cell damage by capturing free radicals or converting them into more inert forms (Borges et  al.  2013; Dawidowicz et al. 2021).

17.5.1  Acute Pain It is important to consider what ECS receptors are upregulated in different pain states and disease processes. In acute pain states, the CB2 receptor is upregulated as it increases up to 100x fold in response to tissue injury and inflammation. The selection of phytocannabinoids and terpenes that elicit anti-­inflammatory and analgesic effects, and/or target the CR2 receptor would be considered most beneficial. Molecules included in this profile include THCA, CBDA, CBD, CBGA, CBG, myrcene, limonene, and beta-­caryophyllene (Mosley et al. 2021). However, in some acute pain settings, the CB1 receptor plays a role as well. Rodent acute pain models measuring inflammation and thermal nociception via planter/ tail flick and heat models suggest that antinociceptive properties exist with cannabinoid administration (Guindon and Hohmann 2007) Recent studies in dogs have shown contradictory results using the same CBD/CBDA product but at different dosing regimens. A higher dosing profile (5 mg/kg) produced lower pain scores following the surgical intervention of IVVD (intervertebral disc disease), while no significant differences in pain scoring between

17.5 ­Cannabinoid Role in Pain Management

the cannabis and placebo groups followed tibial plateau leveling osteotomy (TPLO) surgery (Wright  2022; Di Salvo et  al.  2023; Klatzkow et  al.  2023). Further research is required to determine the specific role of cannabis in acute pain settings; however, the known antinociceptive and synergistic effects of the ECS, endogenous, and exogenous cannabinoids could be considered a welcome addition to a multimodal analgesic treatment regime to decrease the burden and possible adverse side effects of pharmacological agents.

17.5.2  Chronic Pain Chronic pain is a physiologically complex and challenging disease process requiring pharmacological targeting of multiple receptor types. Maladaptive, cancer pain, chronic and neuropathic pain can upregulate a multitude of receptors including NMDA (N-­methyl-­d-­ aspartate), AMP (adenosine 5-­monophosphate), TRPV1, and both CB1 and CB2 endocannabinoid receptors (Mosley et  al.  2021). To date, multiple scientific studies have been published discussing the clinical effect exogenous cannabinoids, particularly CBD, has in the treatment of pain associated with OA in dogs. Each study varied in product molecular composition and multiple dosing profiles were used; however, overall, the studies indicated a reduction in patient pain scores, as well as improved activity level and QOL (quality of life) (Gamble  2018; O’Brien and McDougall  2018; Kogan et al. 2020; Verrico et al. 2020; Brioschi et al. 2020; Mejia et al. 2021; Di Salvo et al. 2023). In one study increased mobility and lower pain scores were observed at doses as low as 0.3 mg/kg, with the average dose range being 1–2 mg/kg every 12 hours, confirming effective analgesia by ECS activation from previous dosing in pharmacokinetic and clinical OA studies (Kogan et  al.  2020). As with acute pain management, the addition of cannabinoids to a patient’s multimodal treatment protocol can contribute to synergy and a decrease in pharmaceutical drug dosing. The confounding physiological processes with chronic pain may

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also be why we see better efficacy in using cannabinoids in these patient populations compared to acute pain.

17.5.3  G-­Coupled Protein Receptors (GPR) G-­coupled protein receptors (GPRs) play a critical role in the pathophysiology and modulation of pain, particularly in pain transduction (Li et  al.  2017). Endocannabinoids anandamide and 2-­AG, as well as phytocannabinoids including THC and CBD, activate GPR 55, which is prevalent throughout the nervous ­system, including large DRGs (Lauckner et  al.  2008; Lu et  al.  2013). The physiological effects of GPR55  within the central nervous system are still being researched, but peripheral activation of this receptor in humans ­contributes to the proliferation and migration of carcinogenic cells, neuroprotection, pain, inflammation, and seizure control (Pérez-­ Gómez et  al.  2013; Marichal-­Cancinoa et al. 2017; Blanton et al. 2022).

17.5.4  Glycine Receptors (GlyR) Implicated in pain sensation, glycine is an amino acid that functions as a neurotransmitter and is the most widely distributed inhibitory receptor in the central nervous system. The central expression of GlyR is in the brainstem and spinal cord, with documentation of pre-­ and postsynaptic receptor distribution. Endocannabinoids AEA and 2-­AG, and phytocannabinoids THC and CBD have shown to either potentiate or inhibit certain glyR ­subtypes, which can result in cannabinoid-­ induced analgesia (Wei et al. 2011; Zhang and Xiong 2013; Anthony et al. 2020).

17.5.5  N-­Methyl-­d-­Aspartate (NMDA) Receptor Glutamate activity on the N-­methyl-­d-­ aspartate (NMDA) receptors in the spinal cord results in increased nociception, decreased opioid receptor response, and increased

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c­ entral sensitization (Bennett 2000; Dedek and Hildebrand  2022). To decrease the upregulation of NMDA receptors and their contribution to the pain cascade, endogenous cannabinoids are liberated. The reuptake inhibitory effects of CBD on AEA decrease glutamate release, and THC antagonism of the NMDA receptor results in a decrease in patient central sensitization (Klein et  al.  2000; Rodríguez-­Muñoz et al. 2016).

17.5.6  Peroxisome Proliferator-­activated Receptors (PPAR) PPARs are a ligand-­activated receptor family located within the cell nucleus. This unique receptor group is capable of directing or ­modifying gene transcription, regulating energy homeostasis, cytokine production, and enhancing glucose metabolism (Klein et al. 2000; Begg et al. 2005; Di Marzo and De Petrocellis 2013; Di Marzo and Piscitelli 2015; Di Marzo  2018). PPARy (peroxisome proliferator-­activated receptors gamma) plays a key role in the inflammatory process by balancing the production of inflammatory cytokines such as TNF-­α (tumor necrosis factor alpha), IL-­6/IL-­12 (interleukin 6–12), and free radicals. The physiological importance of PPARy activation via AEA, 2-­AG, or THC receptor binding includes anti-­inflammatory, neuroprotective factors, and the downregulation of free radical production (Klein et al. 2000; Burston and Kendall 2013; Iannotti and Vitale 2021).

The ECS modulates the hypothalamic-­ pituitary-­adrenal (HPA) axis, which plays a crucial role in the pain/stress relationship, allowing the HPA axis to return  to a nonstressed state (Zhang and Xiang 2013; Hillard et al. 2016; Copas et al. 2021).

17.5.8  Transient Receptor Potential (TRP) Cation Channel Superfamily TRP vanilloid subtypes are members of the TRP cation channel superfamily. This family of receptors are primarily located on peripheral sensory neurons and within the central nervous system. The upregulation of this receptor group is in response to tissue damage and inflammation, via chemo, thermo, or mechanosensation (González-­Ramírez et al. 2017; Mosley et al. 2021). Interaction of the ECS and cannabinoid ligands with vanilloid and melastatin receptors can reduce nociception through modulation of ascending and descending pain pathways. Reduction in nociceptive sensory neurons via anandamide’s agonist activity at TRPV1 has been documented to contribute to analgesia (Muller et  al.  2020). AEA interrupts the inflammatory cascade through inhibition of neurotransmitter release from the presynaptic neuron (Copas et al. 2021). CBD, CBG, CBGV, and THCV are examples of phytocannabinoids capable of desensitizing receptors within the TRP family (Di Marzo and De Petrocellis 2013).

17.5.7  Serotonin Receptors (5-­HT)

17.5.9  Opioids and Opioid Receptors (OPD1, OPK1, OPM1)

Serotonin receptors have significant distribution throughout the peripheral and central nervous system, with increased density in limbic regions of the brain including the hippocampus, hypothalamus, prefrontal ­cortex, and amygdala. Phytocannabinoid binding of major cannabinoids like CBD and THC to 5-­HT receptor sites can produce pathophysiological responses, including anxiety reduction.

Studies of the interaction between the ECS and opioid receptors (delta, kappa, and mu) show synergy and potentiation that exists between the two systems after either opioid or phytocannabinoid delivery, or both (Tham et  al. 2005). With similar mechanisms of action and proximity of receptor locations in the brain and dorsal horn of the spinal cord and at supraspinal levels, the correlation of

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17.6 ­Cannabis Safety and the Veterinary Technicians Role in Client Educatio

the two systems is being extensively researched. Increased expression of endocannabinoid receptor CB1, and to a lesser extent CB2, is increased after opioid administration. Conversely, there is an enhancement of the endogenous opioid system after cannabinoid administration, specifically noted is the upregulation of mu and delta opioid receptors due to allosteric modulation that CBD and THC have at these sites (Tham et  al. 2005; Miranda-­Cortés et  al.  2023). In patients receiving concurrent administration of phytocannabinoids and opioids, the synergistic connection between these receptors may require a reduction in pharmacological opioid doses (Copas et al. 2021; Mosley et al. 2021).

17.5.10  Acetaminophen and the ECS There has been much discussion over the years regarding the mechanism of action of acetaminophen (known as paracetamol in Europe) and its use in canine species in veterinary medicine. Acetaminophen was previously thought to have significant anti-­inflammatory properties and in some literature was labeled a COX-­3 inhibitor. Acetaminophen should not be classified as an NSAID and can safely be given with traditional NSAIDs and cannabinoids (Chandrasekharan et  al.  2002). More recently, it has been postulated that the metabolite of acetaminophen, N-­arachidonoylphenolamin, exhibits activity as an endocannabinoid reuptake inhibitor, and a CB1, CB2, and TRPV1 receptor agonist (Mosley et  al.  2022; Ohashi and Kohno  2020). N-­arachidonoylphenolamin inhibits the degradation of anandamide, ­subsequently prolonging the endocannabinoid’s anti-­inflammatory and analgesic properties (Silver 2019).

17.5.11  Gabapentinoids The synergist effects of gabapentin and cannabis have been established in both human and veterinary medicine. Gabapentinoids, which include pregabalin, have been documented to interact with subunits of voltage-­gated calcium

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channels (VGCCs), mediating voltage-­ dependent Ca2+ influx, therefore reducing excitatory neurotransmitter expression (Di Cesare et al. 2023). It is postulated that the inhibition of VGCC via endocannabinoid activation of G-­protein receptors can contribute to analgesia as well. Pharmacokinetic interaction of CBD contributes to increased gabapentin concentrations as well as mutual serotonergic system interaction, leading to increased sedative effects observed when gabapentin and cannabis are co-­administered (Mosley et al. 2021). A neuropathic pain study in mice observed that co-administration of gabapentin and THC contributed to a reduction in both mechanical and cold allodynia for those affected by chronic constrictive injury (CCl). Importantly, the study observed that the synergy of gabapentin and THC combination enhanced analgesia and allowed for an increased therapeutic window over that of THC administration alone (Atwal et al. 2018).

17.6  ­Cannabis Safety and the Veterinary Technicians Role in Client Education To provide science-­based cannabis education, one must be knowledgeable in the fundamental differences between hemp and cannabis. While hemp is a type of cannabis, it is legally defined as a cannabis plant that contains less than 0.3% THC by dry matter weight at the time of harvest, in the United States and other countries. Non-­hemp cannabis – or marijuana as it’s known recreationally – is a cannabis cultivar that contains more than 0.3% THC at dry matter weight at the time of harvest. Hemp historically has been commercially grown for agricultural purposes such as phyto-­ remediation and deterring insects, as well as for the purpose of food, textiles, construction materials, and furniture. However, the hemp industry has evolved over the years, with growers investigating chemovars to cultivate plants that are beneficial for medical purposes

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(Silver et  al.  2021). Cannabis plant energy is focused into the production of flowers and leaves that contain trichomes. Trichomes materialize on flowers and sugar leaves of mature female plants and produce resin. Resin is considered the most valuable part of the plant and delivers important medicinal molecules such as cannabinoids (major and minor), terpenes, and flavonoids. In Canada, the regulation and licensing of commercial hemp cultivation is through Health Canada, while the Hemp Farming Bill of 2018, under the United States Agricultural Act, is the governing body within the USA. In Canada, as of early 2023, cannabis (cultivars having greater than 0.3% THC) is legal, though highly regulated by the federal government through the Cannabis Act. The Cannabis Act was initiated in October of 2018, legalizing the acquisition, possession, consumption, and cultivation of cannabis and its by-­products. To date, there are no cannabis products approved by Health Canada for use in veterinary patients, nor are veterinarians able to prescribe cannabis to pets unless they are prescribing a drug approved for human use, such as Sativex, in an extra-­label drug use manner. Veterinarians may legally recommend Health Canada approved veterinary health products (VHP), which generally consist of hemp seed derivatives containing no more than 10  ppm THC and are not required to be regulated under the Cannabis Act. Veterinary health products do not contain concentrated phytocannabinoids, including CBD, do not make health claims, and are designated for animal use by a Notification Number (Government of Canada, Health Canada). All health products containing naturally occurring phytocannabinoids are required to be listed under the Human and Veterinary Prescription Drug List. To date, there are no hemp or cannabis-­derived products containing cannabinoids approved for pets in Canada. However, with the planned 2023 review of the Federal Cannabis Act, the veterinary community is lobbying for species-­ specific cannabis products and for

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veterinarians to legally be able to prescribe cannabis for pets. As discussed, knowledge surrounding hemp and cannabis (marijuana) plants is essential when it comes to legalities, client communication and patient documentation. In the United States, the Farm Bill  – Federal Agriculture Improvement Act of 2018  – allows hemp-­ derived CBD, containing less than 0.3% THC dry matter weight at the time of harvest, to be sold by commercial businesses. The removal of hemp from the Controlled Substance Act (CSA) validates that hemp is no longer defined as a controlled substance under federal law in the United States (US Food and Drug Administration 2020). The changes of 2018 have contributed to a significant increase in sales of over-­the-­counter supplements labeled as “CBD pet products.” In most states, depending on marketing and labeling, CBD-­derived hemp products are considered a pet supplement and not a nutraceutical, making it federally legal, reliant on the product complying with the Federal Food, Drug, and Cosmetics Act. These products are not approved or regulated by the Food and Drug Administration Center for Veterinary Medicine, and therefore it is pet owners’ responsibility to confirm quality assurance and safety by requesting and analyzing the product’s certificate of analysis (COA) (Andre et al. 2020). Under US federal law, cannabis (plants and derivatives that contain greater than 0.3% THC on a dry weight basis) are classified as a Schedule 1 controlled substance. The description of this classification makes it illegal to possess, use, or sell cannabis. To date, there are no cannabis products labeled for veterinary species that have been approved by the FDA, and neither cannabis, nor hemp-­derived cannabinoids can legally be prescribed by a veterinarian. Epidiolox® is a purified CBD product labeled for human use and could be prescribed for animals, although it would be extremely cost prohibitive for most owners, where studies comparing efficacy of this FDA-­approved product to quality over-­the-­counter products appear the same if not better.

17.7 ­Harm Reduction Education (HRE

17.7  ­Harm Reduction Education (HRE) Harm reduction is a set of practical strategies and ideas aimed at reducing negative consequences associated with behaviors known to have inherent risks. Harm reduction education (HRE) should be safety-­focused and science-­based, as there is clear evidence supporting the inherent risks of client-­initiated cannabis administration without veterinary oversight. HRE includes the use of appropriate scientific terminology and the fundamental distinctions between molecular properties, hemp and cannabis products, contraindications, concurrent pharmacological interactions and adverse events. The important role of HRE and client education is also provided by cannabis-­educated, licensed veterinary technicians, preferably under the supervision of their ­veterinarian through which the VCPR (veterinary-­client-­patient-­relationship) exists. The significance of this guidance is important because of the overwhelming amount of mislabeled and unsafe over-­the-­ counter products. An FDA investigation in 2020 examined 102 CBD product claims compared to the results of government testing. Of the 102 tested products (Evans 2020), 18 products contained less than 80% of the amount of CBD indicated, 38 products contained more than 120% of the amount of CBD indicated, and an astounding 49% of the CBD labeled products tested contained THC! Furthermore, several unregulated products have been shown to contain heavy metals, pesticides, and residual solvents from extraction, furthering the significant health concerns this can impose on humans and pets (Russo 2019; Brutlag 2021). For the health and safety of our pets, using Health Canada approved recreational products, or those products whose company can provide a third-­party laboratory COA, ensures appropriate testing and laboratory analysis for detection of heavy metals, pesticides, microbes, residual solvents, and the percentage of the quantity of THC,

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CBD, and their acidic formulations (THCA/ CBDA) (Russo 2019; Silver 2021).

17.7.1  THC Intoxication Accidental THC exposure, or over exposure by means of inappropriate dosing, of pets has increased since the legalization of recreational products. Many of these toxicities come from the inadvertent ingestion of edibles or the remnants of cannabis cigarettes that have been irresponsibly discarded. The Pet Poison Control Hotline & SafetyCall International, which serves Canada and the USA, saw a 96% increase in accidental ingestion of cannabis and synthetic cannabinoids in 2020 compared to 2019, and a 108% increase in 2021 compared to 2020 (Pet Poison Hotline 2022). The LD 50 (median lethal dose) of THC has not yet been established. A documented study from 1972 administered a single oral dose of delta 9-­THC and delta 8-­THC between 3000 and 9000/mg/kg with no reported deaths in canines and non-­ human primates (Thompson et al. 1973). It is suspected that the LD50 is greater than 3–9 g/ kg, with no reported deaths in humans, that can be directly attributed to THC or other phytocannabinoids without concurrent administration of other toxic substances. After oral ingestion in dogs, Pet Poison Hotline documented clinical signs starting at 0.3–0.4 mg/kg THC. However, accuracy in dosing is challenging due to the minimal regulatory oversight in many cannabis products. As previously discussed, canines differ from other species in that they have an abundance of CB1 receptors in the brain stem, cerebellum and medulla oblongata (Herkenham et al. 1990; Freundt-­Revilla et al. 2007; Silver 2019; de Andrade et al. 2022). The higher distribution of this cannabinoid receptor in canine hindbrain structures contribute to a neurological condition in which the patient rigidly stands and rocks back and forth. This THC reaction is referred to as “static ataxia” (Silver et  al.  2021). Typical clinical recovery time after THC ingestion is within 24 hours in most cases but there have been reports of up to

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72 hours (Brutlag 2021). Clinical signs of THC toxicity can include: sedation, ataxia, tremors, hyperesthesia, hypothermia, bradycardia, hypotension, and urinary incontinence. A 2020 study in dogs on the safety of escalating cannabinoid dosing with the CBD oil being dosed up to approximately 62  mg/kg, the THC oil dosed up to approximately 49  mg/kg and the CBD/THC being dosed at approximately 12 mg/kg for the CBD and approximately 8 mg/ kg for the THC with lethargy, ataxia, and hypothermia noted in the oils containing THC (Vaughn et al. 2020). Treatment for THC toxicity can include decontamination through emesis and activated charcoal, and, where applicable, intravenous lipid therapy, but most patients recover with supportive care and thermoregulation assistance (Brutlag 2021).

17.7.2  Cognitive Perception Modulation As previously discussed, the endocannabinoid receptor distribution throughout essential centers of the brain, including the prefrontal cortex, amygdala and hippocampus, effects a multitude of behaviors ranging from one’s emotional responses, memory, anxiety and fear, and sleep management – to name a few (Di Marzo and Silvestri  2019; Silver  2021). A veterinary patient inadvertently exposed to elevated doses of THC can experience intoxicating adverse events and cannabinoid-­induced CNS effects, including but not limited to CNS depression, agitation, heightened sensitivity to movement and sounds, urinary incontinence, and ataxia (Brutlag  2021). Recognizing the myriad of cognitive impairments and perception modulation our veterinary patients endure post THC toxicity, it is imperative that appropriate product selection and dosing, as well as safe storage of all cannabis products, is ensured.

17.7.3  Product Guidance For additional assurance of product safety, a COA should be provided by the product company upon request. A COA is a document

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supplied by a licensed laboratory ensuring product safety and potency. A complete COA should include the full cannabinoid profile, CBD:THC ratio, terpene analysis, microbiological testing, heavy metal testing, herbicide, fungicide and pesticide testing, mycotoxin testing, residual solvent testing as well as water and moisture (Russo  2019; Andre et  al.  2020; Silver  2021). Unfortunately, the product label offers minimal information regarding the purity and safety of what is inside. In the authors’ experience, most product labels include the distinction as a hemp or cannabis product, the CBD and THC ratio, usually the mg/g concentrations, and in some instances the carrier oil and extraction method. Pertinent information including minor cannabinoids, terpene and flavonoids concentrations, nonmedicinal ingredients including carrier oils, and the molecular extraction method is typically not listed on the product label. Practitioners, and those technicians comfortable discussing cannabis, need to be competent in reading and understanding a COA to ensure patient safety and appropriate veterinary oversight. Contraindications of cannabis administration include young, pregnant, and lactating patients due to the ongoing development and maturing of the ECS. Precautions should be taken when administering THC to patients with significant cardiac disease due to the risk of dose-­dependent arrhythmias, heart rate and hemodynamic changes (Subramaniam et al. 2019; Du et al. 2019; Brutlag 2021). There is no veterinary research to date on cannabis administration in kidney patients; however, renal impairment can affect the CYP450 Pathway (Cytochrome P450) through which CBD and THC are metabolized, resulting in elevated cannabinoid plasma levels. Human research shows cannabinoids are generally safe to be administered to those patients with chronic kidney disease (MacCallum et al. 2021). Cannabinoid administration, particularly CBD, has been documented to interact with many pharmaceuticals by altering the

17.7 ­Harm Reduction Education (HRE

metabolism of 60–70% of these drugs. Cannabis can cause the induction or inhibition of the CYP450 pathway, a system of proteins that play a key role in the metabolism of drugs and endogenous substrates. Induction of CYP450 can take several days and lead to a decrease in drug plasma concentration and increase metabolism and therefore decrease in drug effect. CYP450  inhibition can happen relatively quickly and cause an increase in drug plasma levels due to inhibition of the enzymes that metabolize the prescription drug where adverse events may be observed (Copas et  al.  2021). Clinically, the author has observed  increased levels of sedation when patients are on concurrent administration of  gabapentin or anticonvulsants with ­cannabinoids. Gabapentin and cannabinoid co-­administration produces analgesic synergy (Copas et  al.  2021;Mosley et  al. 2021; Polson et  al.  2021) by having similar receptor action VGCCs, which could explain the notable increase in sedation. Pharma­cokinetic (PK) changes related to metabolism could also contribute to elevations in gabapentin or anticonvulsant sedation levels. In the author’s experience, many veterinarians choose to mitigate sedative side effects by decreasing the dose of the pharmaceutical agents while continuing the administration of the cannabis product. Concurrent administration of cannabinoids with ketoconazole or dexamethasone have been shown to produce an increase in the active and inactive forms of cannabinoids due to activity at the CYP450 pathway. Benzodiazepines’ action on the GABA receptor can be altered by cannabinoids, potentiating the risk for intoxication-­ like symptoms. For a complete list of cannabinoid interactions, visit drug-­http:// interactions.medicine.iu.edu.

17.7.4  Dosing An essential aspect of HRE is appropriate therapeutic dosing. The scientific literature documenting cannabis administration in animals is increasing, as does the education regarding therapeutic dosing considerations. As of 2023,

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there are well over a dozen published pharmacokinetic (PK) studies in small animals, exotics, and large animals. Additionally, in dogs there are multiple safety studies of CBD dominant products, and three similar studies in cats. Canine and feline studies have discussed dosage ranges from 0.25 to 2 mg/kg every 12 hours (Deabold et al. 2019; Vaughn et al. 2020; Vaugh et  al.  2021; Kulpa et  al.  2021; Chicoine et al. 2020; Morris et al. 2022). In the author’s experience, the most effective route to administer cannabinoids in veterinary patients is through transmucosal or oral techniques. Cannabinoid molecular absorption can be influenced by a multitude of factors including the formulation, integrity of the gastrointestinal system, volume administered, and if that patient has received a meal prior to treatment. Foods with linoleic acid will significantly increase bioavailability (Sharma et  al.  2012; Deabold et  al.  2019; Verrico et al. 2020; Wakshlag et al. 2020). Common carrier oils in human and veterinary medicine are MCT (medium chain triglycerides), hemp seed, and pumpkin seed oil. Some veterinary patients may experience diarrhea as an adverse reaction to a carrier oil. In the author’s experience, clients may then choose to switch to a product with a similar molecular profile but a different carrier oil. The difference between oral and transmucosal administration comes down to product volume, patient preference and compliance. Human and canine pharmacokinetic studies involving the bioavailability of orally and transmucosal administered CBD and THC range from 13% to 35% (Lebkowska-­ Wieruszewska et al. 2019; Russo 2019; Vaughn et al. 2020; Cital 2020). From a PK perspective, one would postulate that oral administration would provide less bioavailability due to first-­ pass metabolism, however, that has been proven to not be the case. Depending on the concentration of the tincture, transmucosal administration can be challenging due to the substantial volume of a particular product. Recent human studies and to extent canine studies postulate that a small volume of a high fat meal may increase the bioavailability and

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cannabinoid plasma level concentration in the blood, particularly that of CBD (Zgair et  al.  2016; Russo  2019; Deabold et  al.  2019; MacCallum et al. 2021; Amstutz et al. 2022).

17.7.5  Monitoring There is still some uncertainty surrounding the long-­term effects of cannabis therapy in the literature. However, anecdotal evidence from clinical use in animals and humans suggests relative safety. To mitigate the risk of adverse effects, it is important that a baseline general health blood profile be performed prior to initiating cannabis therapy. Documented changes in alkaline phosphatase (ALP), without alterations in liver function, have been observed in canine populations being administered CBD dosages at or above 2  mg/kg. ALP elevation may also be noted in patients who are receiving concurrent pharmaceuticals that alter liver metabolism or increase hepatic stress. ALP in isolation is clinically uninformative without other liver biomarkers also being out of normal ranges (Di Marzo 2020; Andre et al. 2020; Brutlag 2021). Bradley et al. (2022) with the hypothesis postulated by Stephen Niño Cital, found ALP increases were not only derived from the liver but also bone, suggesting increased bone tissue growth and turnover. Cannabinoids are being investigated for women as a treatment for ­osteoporosis and have also been used to regrow bone in rodent models. Repeat hepatic and renal values in patients who have started cannabinoid therapy are suggested at 1 month and then 3–6 months after reaching target dosing tend to be a standard cannabis monitoring protocol (Freedman and Patel 2018; Cital 2020). The notable increase in veterinary clients seeking current, science-­based cannabis information from veterinary professionals is only in its infancy. In the author’s opinion, cannabinoid therapy in veterinary medicine is progressing in a positive direction, but continued support through validated scientific research is

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imperative to keep up with the evolution of cannabis within the veterinary community. There is a continued demand for transparency and standardized guidelines surrounding the manufacturing, production, testing, and labeling of hemp and cannabis products. As we have celebrated the evolution of science surrounding cannabis within the human medical field, it is essential for veterinary cannabis organizations, veterinary and technician associations, as well as pet parents to continue to advocate for, and lobby governments, to grant veterinary access to cannabis. This includes most importantly, but not limited to, the legal recommendation and prescription of safe and effective veterinary-­specific products. There is a continued effort of veterinary cannabis organizations and cannabis-­trained veterinary professionals to continue to improve patient QOL through evidence-­based cannabis applications while advocating for veterinary and pet parent accessibility to safe and effective cannabinoid therapy.

17.8  ­Acupuncture Acupuncture, from a Western medicine standpoint, entails the insertion of thin needles into precise anatomical locations on the body, such as nerve branch points or neurovascular structures within tissues. Its primary objective is to trigger an internal response that fosters pain relief, healing, and immunomodulation. More recently, it has also been shown that the ECS can be upregulated by acupuncture. Additionally, acupuncture has been observed to enhance blood circulation, suppress inflammation, alleviate muscle tension, recalibrate proprioceptive mechanisms and posture, and influence the autonomic nervous system. This occurs, in part, through local spinal inhibition of nociception, the release of endogenous opioids within the spinal cord, and the activation of inhibitory interneurons and descending pathways that mitigate pain signals (Figure 17.3).

17.9 ­Supplements for Pain Management

extrapolated from human points that were developed over thousands of years. As the animal interstitium is further defined among species, we may be able to find more effective points or techniques (Benias et al. 2018; Zhang et  al.  2018; Tomov et  al. 2020). An editorial from 2013 published in the human journal Anesthesia & Analgesia concluded, “It is clear from meta-­analyses that results of acupuncture trials are variable and inconsistent, even for single conditions. After thousands of trials of acupuncture and hundreds of systematic reviews, arguments continue unabated.”

17.9  ­Supplements for Pain Management Figure 17.3  Acupuncture being performed by a veterinary technician. Source: Courtesy of Stephen Niño Cital.

It is important to note that acupuncture is a multifaceted intervention that demands specialized training. Its clinical applications encompass a variety of conditions such as spinal cord injuries or diseases, wounds, chronic pain like OA, visceral pain, and myofascial trigger point pain. From a Chinese medicine perspective, acupuncture helps balance or allows for appropriate movement of “Qi” or the body’s energy flow. Interestingly, the discovery of the interstitium, a new organ discovered in 2015 (first described in a scientific report in 2018), may bridge the “why” and “how” acupuncture can work in many patients. As far as the clinical trials in animals are concerned, the data is mixed. Quality placebo controlled scientific studies in animals generally lack proving efficacy, yet anecdote suggests benefit. In human studies, the data is split almost evenly (Monteiro et  al.  2022; Gruen et  al.  2022). However, despite the lack of overwhelming scientific data to support acupuncture in animals, the discovery of the interstitium may allow us to reevaluate the current points used, which were largely

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Animal supplements or nutraceuticals are a largely unregulated industry. Most animal supplements have little to no clear scientific studies to support dosing or efficacy of the ingredients with a few exceptions, like omega­3 fatty acids. Nor are any animal supplements FDA approved. Here we describe the animal health supplements that do have some scientific evidence while also sharing which other common supplements used in animals have been disproven (Finno 2020).

17.9.1  Omega-­3 Fatty Acids Omega-­3 PUFA, particularly eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are well-­studied for having anti-­inflammatory properties by inhibiting the metabolism of arachidonic acid into eicosanoids, prostaglandin, and leukotriene. Additionally, there is research suggesting EPA and DHA can positively influence the diversity of the gut microbiota (Constantini et al. 2017; Tagne et al. 2021). OA is a condition that can benefit from the supplementation of omega-­3 fatty acids. In normal canine cartilage, there is a balance between synthesis and degradation of the cartilage matrix. In arthritic joints, damage to chondrocytes incites a vicious circle that culminates in

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the destruction of cartilage, inflammation, and pain. The mechanisms responsible for the demonstrated clinical benefits of omega-­3 fatty acids include controlling inflammation, thereby aiding in the management of pain and reducing the activity of cartilage-­degrading enzymes, which slows the progression of the disease. Degradation of ­cartilage starts with loss of cartilage proteoglycan, which is followed by loss of cartilage collagens. This results in the loss of the ability to resist compressive forces during joint movement. EPA is the only omega-­3 fatty acid able to significantly decrease the loss of proteoglycan in the canine cartilage in vitro model. In canine cartilage, EPA inhibits the upregulation of aggrecanases by blocking the signal at the level of messenger RNA, thus altering gene expression and the progression of disease in these patients. Ingestion of foods containing omega-­3 fatty acids results in a decrease in membrane arachidonic acid (AA) levels because omega-­3 fatty acids replace AA in the substrate pool. This produces an accompanying decrease in the capacity to synthesize inflammatory eicosanoids from AA. High levels of omega-­3 fatty acids can depress inflammatory eicosanoids produced from AA in dogs. In addition to their role in modulating the production of inflammatory eicosanoids, omega-­3 fatty acids have a direct role in the resolution of inflammation. The absence of sufficient dietary levels of omega-­3 fatty acids may contribute to “resolution failure” and perpetuation of chronic inflammation. In cats, DHA rather than EPA (as used in dogs) inhibits the aggrecanase enzymes responsible for cartilage degradation (Burns and Towell 2011).

17.9.2  Palmitoylethanolamide (PEA) PEA is an endocannabinoid-­like lipid mediator belonging to the N-­acyl-­ethanolamine (NAE) fatty acid amide family with extensively documented benefits in animals. Through unique mechanisms of action and multiple different pathways, PEA can provide anti-­inflammatory, analgesic, antimicrobial, immunomodulatory, and neuroprotective actions. Indirectly, PEA

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activates CB1 and CB2 through a phenomenon known as the entourage effect. Due to its high lipophilic nature, almost complete insolubility, and thus poor digestibility this supplement has only recently been available as an oral nutraceutical (Clayton et al. 2021).

17.9.3  Turmeric (Curcumin) Turmeric is an ancient spice used commonly in South Asian cooking and has been suggested as a remedy for arthritic pain Innes et al. (2003). Its exact mechanism of action is still unknown, but some research suggests its effects are via the TRPV receptor. Turmeric root has a long history in Ayurvedic medicine, where it is utilized both as a spice and for its potential in modulating immune-­inflammatory diseases affecting various parts of the body, particularly in regions where turmeric is commonly consumed. Turmeric boasts over 235 active components, including essential oils, curcuminoids (with more than 89 varieties), and turmerosaccharides, in addition to curcuminoid-­free constituents and dietary fiber. These phytochemicals, alongside fiber and their by-­products produced through microbial breakdown, may cooperate in a way that helps regulate persistent immune inflammation and pain seen in horses, pets, and humans Kępińska-­Pacelik and Biel (2023). Preliminary evidence suggests that using low doses of turmeric or its active component, ­curcumin/curcuminoids, may have potential applications in preventing or managing immune-­inflammatory conditions in the eyes, brain, joints, and gut for both pets and people. The introduction of standardized turmeric (pharmaceutical grade) is a relatively new development and may potentially reduce the necessity for analgesics (such as opioids), antidepressants, steroids, and even anticancer medications. Utilizing advanced drug-­targeted delivery methods and conducting dependable clinical trials is still necessary and have not been performed in companion animals (Gupta et al. 2013; Kępińska-­Pacelik and Biel 2023).

17.9 ­Supplements for Pain Management

It’s important for consumers to be vigilant regarding the potential adulteration of turmeric and its extracts. Using turmeric as a spice in food at low doses is generally safe for consumption, however, higher doses may lead to gastrointestinal upset and function, resulting in symptoms like nausea, diarrhea, and vomiting (Innes et al. 2003). Safety assessments, as summarized by Gupta et al. in 2013, indicate that curcumin is safe for a range of species, including rodents, primates, horses, rabbits, cats, and humans. Curcumin does have the ability to inhibit the activity of drug-­metabolizing enzymes, such as cytochrome P450, GST, and UDP-­glucuronosyltransferase, in laboratory settings and animal models. Consequently, there is a possibility of drug interactions when curcumin is used alongside medications like acetaminophen, digoxin, and morphine, which could lead to elevated plasma concentrations, potentially raising concerns about drug safety. Additionally, curcumin is known to act as an active iron chelator and can induce anemia in mice when administered in conjunction with iron-­deficient diets. Chronic use may also lead to increased clotting times. Dosing is far from refined and will depend on the purity of the product being used. Doses in the literature are broad from 13  mg total in dogs (Kobatake et  al.  2021), to 4–90  mg/kg orally (Gopinath and Karthikeyan 2018).

17.9.4  Glucosamine/Chondroitin and Undenatured Collagen-­based Supplements Glucosamine and collagen-­based supplements have been used for decades in veterinary medicine. Unfortunately, meta-­analysis studies, which are the top tier of scientific evidence, have shown little to no efficacy. Dosing for ­glucosamine/chondroitin is anecdotal, as will the 10 mg, once-­a-­day suggested dose of undenatured collagen type II products (Liu et al. 2018; Lugo et al. 2015). In fact, Barbeau-­Grégoire et al. (2022) states:

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Our analyses also showed, with studies of lesser quality, a weak efficacy of collagen-­based nutraceuticals and a very marked ­non-­effect of chondroitin-­glucosamine-­based products. The quality of the latter studies is disappointing in terms of concluding on the use of these products, and the total lack of efficacy of chondroitin-­ glucosamine nutraceuticals stands out in comparison with the other categories, and therefore indicates that these products should no longer be recommended in cases of canine or feline OA.

17.9.5  Kratum 7-­Hydroxymitragynine and mitragynine are two of the more prominent active molecules in the kratum plant. In Southeast Asia, kratom has long been used for the alleviation of pain and opium withdrawal. In the West, kratom is increasingly being used by individuals for the self-­management of pain or withdrawal from opioid drugs (Fluyau and Revadigar  2017). Opioid-­like effects, such as analgesia, constipation, euphoria, and sedation, are typically associated with the use of moderate-­high doses of kratom (5–15 g) in humans. The euphoric effects of kratom generally tend to be less intense than those of opioid medications. These special aspects of kratom pharmacology have received the most scientific attention and interest for use as an analgesic. Although to our knowledge, no companion animal clinical studies on the effects of kratom have been published, there is good research animal studies and anecdotal evidence of efficacy and safety (Mat et al. 2023). A clinical study assessing its efficacy in dogs with chronic pain is in process at the University of Florida. One pharmacokinetic study has been performed in dogs with dosing at 5  mg/kg orally (Maxwell et al. 2020).

17.9.6  Magnesium Magnesium and its potentiating effects on peri/post-­operative analgesia and muscle relaxation have drawn attention more recently

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in veterinary medicine. Continuous rate infusions, epidurals of magnesium alone and in combination with other analgesics, and to an extent oral supplementation of magnesium enable anesthetists to reduce the use of ­traditional anesthetics during surgery and the use of analgesics after surgery. Magnesium ­sulfate has a high therapeutic index and ­cost-­effectiveness. The magnesium ion is responsible for keeping the NMDA receptor (one of the receptors responsible for wind-­up and neuropathic pain) cool, calm, and collected. In humans, it is not uncommon for circulating levels of magnesium to be deficient postoperatively. Although not proven, it is speculated this phenomenon may occur in veterinary species as well. Concerns of creating hypermagnesemia with supplementation are low as long as the patient has sufficient renal function (Bilir et  al.  2007; Viilmann and Vettorato  2021; Bahrenberg et  al.  2015). However, a meta-­analysis by Debuigne et  al. (2024) found the evidence at hand to be low-­ quality, and there is a general paucity of veterinary-­specific evidence.

17.9.7  Green Lipped Mussel Extract Extracts of the New Zealand green-­lipped mussel have been used since the 1970s for the treatment of both rheumatoid arthritis and OA in humans. It has also been used in veterinary medicine with increased frequency. The anti-­inflammatory properties are now well proven in studies dating back to the 1980s. These studies demonstrated the product’s anti-­inflammatory effects both in  vitro and in vivo, while more recent research indicates that the activity may be largely associated with the N-­3 essential fatty acids eicosatetraenoic acid and dodecaphonic acid, which appear to produce inhibition of the lipoxygenase pathway of the prostaglandin system, thus reducing both inflammation and pain without interfering with normal prostaglandin function, unlike traditional NSAIDs (Coulson et al. 2012). Interestingly, in a meta-­ analysis of joint supplements, green mussel

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extract has one of the longest spans of pain-­ relieving efficacy, though the authors advise there is low-­quality evidence in animals and product quality is of concern. Dosing regimens and recommendations are still not well described (Liu et  al.  2018; Barbeau-­Grégoire et al. 2022).

17.9.8  Passion Fruit Peel Extract Plant terpenoids and flavonoids attenuate inflammation through their inhibition of regulatory enzymes involved in arachidonic acid metabolism. They also inhibit lipoxygenase and cyclooxygenase activities so that their beneficial properties are caused by their anti-­ inflammatory properties. An anti-­inflammatory supplement, such as passion fruit peel (PFP) extract isolated and purified from Passiflora edulis, has also been shown to be free radical scavenging. PFP scored better than many other supplements in the meta-­analysis (Liu et al. 2018).

17.9.9  Avocado/Soybean Unsaponifiables (ASU) Avocado/soybean unsaponifiables are natural vegetable extracts made from avocado and soybean oils. ASUs are composed of one-­third avocado and two-­thirds soybean unsaponifiables. The major components of ASU are phytosterols β-­sitosterol, campesterol, and stigmasterol, which are rapidly utilized by cells. ASU is also a complex mixture of many compounds including fat-­soluble vitamins, sterols, triterpene alcohols, and possibly furan fatty acids, with identities of some active components to be determined. ASU helps modulate OA pathogenesis by inhibiting several molecules and pathways, such as anti catabolic properties preventing cartilage degradation by inhibiting the release and activity of matrix metalloproteinases and increasing tissue inhibitors of these catabolic enzymes. ASU also inhibits fibrinolysis by stimulating the expression of a plasminogen activator inhibitor. Anabolic properties encourage cartilage

17.10 ­Conclusio

repair by stimulating collagen and aggrecan synthesis via inhibition of inflammatory cytokines such as interleukin (IL)-­1, IL-­6, IL-­8, tumor necrosis factor (TnF β), ERK, and prostaglandin E2. Chondroprotective (cartilage) effects are mediated by correcting growth factor abnormalities, increasing TGF-­β, and decreasing vascular endothelial growth factor (VEGF) in synovial fluid (Boileau et al. 2009). ASU also inhibits cholesterol absorption and endogenous cholesterol biosynthesis, which mediate ROS pathology in chondrocytes. At the clinical level, ASU reduces pain and stiffness while improving joint function, resulting in decreased dependence on analgesics in both humans and animals (Liu et al. 2018; Barbeau-­ Grégoire et al. 2022).

17.9.10  Yucca Schidigera Yucca schidigera is a medicinal plant native to Mexico. It has been traditionally used in indigenous medicine for its potential anti-­arthritic and anti-­inflammatory properties. This plant is known to contain various active phytochemicals, including abundant steroidal saponins, which are commercially utilized as a source of saponins. Saponins exhibit a wide range of biological effects, including antiprotozoal activity, leading to speculation that their anti-­arthritic potential could be linked to the suppression of intestinal protozoa, potentially involved in joint inflammation. Yucca is a notable source of polyphenolic compounds, such as resveratrol and various stilbenes like yuccaols A, B, C, D, and E, which possess anti-­inflammatory properties. These compounds act as inhibitors of the nuclear transcription factor NF-­kappa-­B, which, in turn, stimulate the production of inducible nitric oxide synthase, a key factor in the formation of the inflammatory agent nitric oxide. Additionally, yucca phenolics demonstrate antioxidant properties and serve as scavengers for free radicals, potentially contributing to the suppression of ROS that trigger inflammatory responses. Dosing regimens and recommendations are still not well described (Liu et al. 2018).

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17.9.11  Melatonin Research has provided evidence that ­melatonin exerts antinociceptive effects at the spinal cord  and supraspinal levels. The mechanism underlying melatonin’s antinociceptive actions is still not fully understood but is believed to encompass various receptors, including opioid, benzodiazepine, α1-­ and α2-­adrenergic, serotonergic, and cholinergic receptors. Notably, the participation of MT1/MT2  melatonergic receptors within the spinal cord has been extensively established as a mechanism for reducing pain perception in several animal models. Melatonin has been effectively utilized in managing pain associated with medical conditions such as fibromyalgia, irritable bowel syndrome, migraine, and cluster headache (Danilov and Kurganova 2016). Additionally, it has been examined in surgical settings, demonstrating its capacity to enhance both preoperative and postoperative pain relief. In the authors’ experience this is an excellent addition for difficulty to manage pain syndrome such as Chiari malformation associated pain. Dosing is from 1 to 5 mg/kg by mouth once to twice a day in dogs and cats (Srinivasan et al. 2012; Torres et al. 2012; Esposito et al. 2010).

17.10  ­Conclusion Nutrition holds a principal role in the realm of veterinary medicine, affecting every pet that enters the clinic. Among the three fundamental factors that influence an animal’s life  – genetics, environment, and nutrition  – it is nutrition that the veterinary healthcare team, including veterinary technicians and technologists, can actively and directly influence. The utilization of nutraceuticals and animal supplements has a rich history in veterinary medicine. While certain approaches within supplements have demonstrated clear and clinically significant benefits, it is imperative to acknowledge that many others do not offer any tangible advantages and, in some cases, may even pose risks.

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and Cannabinoid Research 1 (1): 113–121. https://doi.org/10.1089/can.2016.0006. Rodríguez-­Muñoz, M. et al. (2016). Endocannabinoid control of glutamate NMDA receptors: the therapeutic potential and consequences of dysfunction. Oncotarget 7 (34): 55840–55862. https://doi.org/10.18632/ oncotarget.10095. Romagnolo, D.F. and Selmin, O.I. (2012). Flavonoids and cancer prevention: a review of the evidence. Journal of Nutrition in Gerontology and Geriatrics 3: 206–238. https://doi.org/10.1080/21551197.2012. 702534. Roychoudhury, P., Wang, N.N., and Narouze, S.N. (2021). Phytocannabinoids: tetrahydro­ cannabinoid (THC). In: Cannabinoids and Pain (ed. S.N. Narouze), 71–77. Switzerland: Springer International Publishing. Russo, E.B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-­ terpenoid entourage effects. British Journal of Pharmacology 163 (7): 1344–1364. https://doi. org/10.1111/j.1476-­5381.2011.01238. x. Russo, E.B. (2019). The case for the entourage effect and conventional breeding of clinical cannabis: no “strain,” no gain. Frontiers in Plant Science 11: http://doi.org/10.3389/fpls. 2020.573299. Russo, E. (2020) ‘Introduction to the Endo­ cannabinoid System’. https://ethanrusso.org. Russo, E. (2021). Forward. In: Cannabis Therapy in Veterinary Medicine: A Complete Guide (ed. S. Cital, K. Kramer, L. Hughston, and J.S. Gaynor). Switzerland: Springer International Publishing. Russo, M. et al. (2015). Sativex in the management of multiple sclerosis-­related spasticity: role of the corticospinal modulation. Neural Plasticity 656582. https://doi.org/10.1155/2015/656582. Salminen, S., Collado, M.C., Endo, A. et al. (2021). The international scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature

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FDA-­cannabis-­regulation (accessed 16 June 2024). Vaughn, D., Kulpa, J., and Paulionis, L. (2020). Preliminary investigation of the safety of escalating cannabinoid doses in healthy dogs. Frontiers in Veterinary Science 11: http://doi. org/10.3389/fvets.2020.00051. Vaughn, D., Kulpa, J., and Paulionis, L. (2021). Randomized, placebo-­controlled, 28-­day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. American Journal of Veterinary Research 82 (5): 405–416. https://doi.org/ 10.2460/ajvr.82.5.405. Verrico, C.D. et al. (2020). A randomized, double-­blind, placebo-­controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain 161: 2191–2202. https://doi.org/10.1097/j.pain. 0000000000001896. Viilmann, I. and Vettorato, E. (2021). Perioperative use of thoracic epidural anaesthesia, dexmedetomidine and magnesium sulphate infusion in a dog undergoing neuroendocrine tumour resection. Veterinary Record Case Reports 9 (4): http://doi.org/10.1002/vrc2.177. Vuckovic, S. et al. (2018). Cannabinoids and pain: new insights from old molecules. Frontiers of Pharmacology, Section Neuropharmacology 9: http://doi.org/10.3389/ fphar.2018.01259. Wakshlag, J. et al. (2020). Cannabinoid, terpene, and heavy metal analysis of 29 over-­the-­ counter commercial veterinary hemp supplements. Veterinary Medicine: Reports and Research (Auckl) 11: 45–55. https://doi.org/ 10.2147/VMRR.S248712. Watson, J.E., Kim, J.S., and Das, A. (2019). Emerging class of omega-­3 fatty acid endocannabinoids & their derivatives. Prostaglandins and Other Lipid Mediators 143: 106337. https://doi.org/10.1016/ j.prostaglandins.2019.106337. Wei Xiong, W. et al. (2011). Cannabinoid potentiation of glycine receptors contributes to cannabis-­induced analgesia. Natural

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Chemistry Biology 7 (5): 296–303. https://doi. org/10.1038/nchembio.552. Williamson, B.G., Jarboe, J., and Weaver, C. (2021). Cannabinoids in neurological conditions. In: Cannabis Therapy in Veterinary Medicine: A Complete Guide (ed. S. Cital, K. Kramer, L. Hughston, and J.S. Gaynor), 143–170. Switzerland: Springer International Publishing. Wright, J. (2022). Evaluating the benefits of cannabidiol for analgesia following surgery for intervertebral disc herniation in dogs. Proceedings of the American College of Veterinary Internal Medicine Forum. American College of Veterinary Internal Medicine (9): 1036056. https://doi.org/10.3389/fvets. 2022.1036056. Yu, L., Yan, J., and Sun, Z. (2017). D-­limonene exhibits anti-­inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-­2, PGE2 and ERK signaling pathways. Molecular Medicine Reports 15 (4): 2339–2346. https://doi.org/ 10.3892/mmr.2017.6241. Zgair, A. et al. (2016). Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-­based medicines. American Journal of Translational Research 8 (8): 3448–3459. Zhang, L. and Xiong, W. (2013). Non-­ psychoactive cannabinoid action on 5-­HT3 and glycine receptors. In: endoCANNABINOIDS: Actions at Non-­CB1/ CB2 Cannabinoid Receptors (ed. M.E. Abood, R.G. Sorensen, and N. Stella), 199–220. New York: Springer International Publishing. Zhang, Z., Leong, D.J., Xu, L. et al. (2016). Curcumin slows osteoarthritis progression and relieves osteoarthritis-­associated pain symptoms in a post-­traumatic osteoarthritis mouse model. Arthritis Research & Therapy 18: 128–140. Zhang, W. et al. (2017). Fatty acid transporting proteins: roles in brain development, aging, and stroke. Prostaglandins, Leukotrienes, and

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https://doi.org/10.1007/s11655-­017-­2791-­3. Epub 2018 Jan 9. PMID: 29327122. Żółkiewicz, J., Marzec, A., Ruszczyński, M., and Feleszko, W. (2020). Postbiotics—­a step beyond pre-­and probiotics. Nutrients 12 (8): 2189. http://doi.org/10.3390/nu12082189.

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18 Pain Management for End-­of-­Life Care Brooke Quesnell1 and Danielle DeCormier 2 1 2

WestVet, Boise, ID, USA MedVet, Whitmore Lake, MI, USA

Providing care for pets with chronic and ­terminal illnesses can significantly transform the relationship between humans and their animal companions, potentially affecting the mental well-­being of the caregiving family. Specifically, when pets approach the end of their lives, their caregivers often experience a profound urge to offer comfort, pain alleviation, and affection, indicating the deep emotional bond they share with their pets (Adams et  al.  2000). The hospice and palliative care system for animals fulfills these emotional needs, and veterinary technicians are ideally positioned and highly critical in fulfilling this mission.

18.1  ­Hospice and Palliative Care Pet hospice care is initiated once a veterinarian or the pet’s family acknowledges the severity of the pet’s illness and the need to prioritize comfort over further curative attempts in the treatment strategy. Palliative care, which is essentially comfort care, can be provided alongside the treatment plan

chosen by the family. This care is delivered by a specialized team and is centered around improving the pet’s quality of life. It should be noted that a pet might have a severe (but not necessarily terminal) disease, and the family may opt for palliative care after fully understanding all the treatment options and the progression of the disease (National Institute on Aging 2021). Hospice services offer compassionate care to individual patients and their families facing critical illness or nearing the end of life, aiming to enhance their quality of life until their death with or without euthanasia, while also providing emotional and mental health support to their families in preparation for the loss. The hospice and palliative care approach is tailored based on the family’s goals and preferences, with input and guidance from the veterinary healthcare team. For a comprehensive understanding of hospice and palliative care, please refer to Dr. Tami Shearer’s 2011 primer, Palliative Medicine and Hospice Care in Veterinary Clinics of North America: Small Animal Practice, vol. 41-­3 (Philadelpia, PA: Elsevier).

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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Regarding daily operations, animal ­hospice and palliative care teams may not have specific titles but are organized to achieve the following goals: 1) Alleviate patient suffering by managing pain and discomfort through medical, physical, and surgical interventions, along with attentive nursing care either at home or in a veterinary facility. These teams are available round-­the-­clock to ensure continuous relief from patient discomfort. 2) Provide emotional support to caregivers, helping them cope with the impending loss of their beloved companion animal. This includes education about grief, validating caregivers’ emotions, and demonstrating empathy and understanding. Such support is delivered through clinic visits, home visits, and various communication channels. The inclusion of veterinary social workers in the healthcare team has proven beneficial in supporting caregivers throughout the end-­of-­life care journey and beyond. 3) Facilitate a journey with minimal regrets, allowing caregivers and their pets to cherish quality time together in familiar, peaceful settings with access to guidance and support as needed. End-­of-­life consultations are instrumental in assisting caregivers in making tough decisions regarding their pets’ care. 4) Ensure a dignified and serene end-­of-­life experience by providing supportive care such as pain relief and sedation during the final hours of the animal’s life. These objectives encapsulate the holistic approach of hospice and palliative care for animals, emphasizing compassion, comfort, and support for both patients and their caregivers.

18.1.1  Veterinary Staff in the Hospice and Palliative Care Environment Hospice and palliative care present distinct challenges and opportunities for veterinary technicians, creating a unique work environment.

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First, technicians must be highly adaptable to new settings that are typically designed for human and animal habitation rather than ­specialized animal nursing care. Observing the environment offers a chance to build stronger relationships and gain a deeper understanding of both the animal and caregiver, which is crucial for providing guidance during difficult decisions. Are there clues to the owner’s religious or spiritual practices? Where is the animal kept, and how integrated does the animal appear to be in the owner’s life? These are unspoken clues that may help guide care recommendations. Second, there is a delicate balance in hospice and palliative care between acknowledging the sadness of illness and impending death while also appreciating the time remaining. It’s important to respect the quality of life that the animal and caregiver can still enjoy. Caregivers often experience anticipatory grief, encompassing various emotions as they care for a loved one nearing the end of life, an experience that shapes them profoundly. Third, hospice environments often present ethical dilemmas, as caregivers may make decisions that differ from what technicians and other providers believe is best for the animal. Navigating these situations requires empathy and compassion while respecting differing perspectives on what constitutes the animal’s best interest.

18.1.2  Work Areas Veterinary technicians work in a variety of settings, with each presenting their own unique challenges and opportunities. Palliative and hospice care can be provided in specialty practice, general practice, and hospice-­specific practice  –­ the last of which is often provided within the caregiver’s home. In specialty practice, veterinary technicians treat patients for their various diseases or interact with the patient on an emergent basis. Those providing specialty care often create intense bonds over short periods of time with the caregivers. Alternatively, emergency-­only

18.2  ­Technicians’ Roles in a Hospice and Palliative Care Practic

visits often lack the bond with the family and rely on a technician’s desire to ease patient discomfort and comfort the caregiver. As part of the lifelong medical team, the general practice technician may have been present for every stage of the life of the patient. Caregivers rely on this team for support throughout the patient’s life and often look to them for guidance at the end of life. The technician’s knowledge and experience in palliative care, especially pain relief, is important to help the caregiver make informed decisions. Working in the caregiver’s home presents distractions and requires the ability to maintain professional conduct outside of a medical facility. It also provides the team with a specific look at the environment the patient is living in. They can make recommendations based on the caregiver’s resources.

18.2  ­Technicians’ Roles in a Hospice and Palliative Care Practice Technicians play an important role in the following aspects of hospice and palliative care practice.

18.2.1  Patient Presentation and Evaluation The initial patient evaluation begins with a comprehensive interview that serves a dual purpose. In this interview, the veterinary technician gathers pertinent information about the patient and the family’s background. This process also involves expressing empathy toward both the patient and the caregiver, showcasing the compassionate and family-­centric nature of the hospice relationship. The veterinary team then performs an assessment and examination of the patient.

18.2.2  Planning of Care Once the initial plan of care has been agreed to by the family and attending veterinarian, a

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hospice team meeting is convened to work out the patient and caregiver’s detailed, individualized plan of care, taking into consideration the family’s background, challenges, resources, and preferences.

18.2.3  Delivery of Care Veterinary technicians are involved in the following aspects of delivering palliative and hospice care. Prescriptions  The veterinarian’s role involves recommending treatment options that are most likely to maintain and enhance the patient’s quality of life, aligning with the caregiver’s beliefs and objectives. It is crucial to minimize the risk of drug interactions and adverse reactions. Consideration should be given to each patient’s unique response to medication, as well as the caregiver’s resources like time, financial capacity, physical ability, and willingness. Depending on the caregiver’s preferences, complementary and alternative treatments may also be integrated into the overall treatment plan. Veterinary technicians play a vital role in conveying the veterinarian’s recommendations to caregivers, ensuring clear understanding and encouraging active participation in imple­menting the treatment plan. Follow-­Up,

Assessment,

and 

Monitoring 

Monitoring is best done by a combination of the following: ●●

●● ●● ●●

Progress reports from the caregivers communicated to the hospice team in person, by phone, or electronically Veterinary technician recheck examinations Veterinarian recheck examinations When applicable, repeated collection of laboratory data

Patient assessment can be performed during the veterinary technician’s hospice home visits.

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18.2.4  Caregiver Education and Training All members of the animal hospice and ­palliative care team contribute to providing caregivers with information and resources. Veterinary nursing staff can undergo training to educate caregivers on various topics such as administering medications, observing animal behavior, assisting with daily activities, recognizing symptoms, and understanding end-­of-­life processes. Veterinary technicians play a vital role in veterinary palliative care by ensuring that caregivers are equipped with the necessary skills to provide optimal care for their animals. This includes training caregivers in various essential tasks: administering oral, rectal, and injectable medications; bathing and arranging comfortable bedding; utilizing support equipment like slings and boots; identifying subtle behavioral signs of pain; managing bladder issues; and repositioning animals that are lying down. Additionally, veterinary technicians are skilled in teaching caregivers about practical aspects of animal behavior and handling. It is crucial to address any task that may be unfamiliar, awkward, or uncomfortable for caregivers. Veterinary technicians demonstrate and practice these tasks with caregivers, providing a supportive environment that helps alleviate anxiety and insecurity. This hands-­on approach allows caregivers to gain confidence in their abilities and ensures that they can effectively carry out necessary care tasks for their animals in a palliative care setting.

18.2.5  Setting Up the Physical Environment Veterinary technicians play a crucial role in veterinary palliative care by offering guidance to caregivers regarding equipment and techniques to maintain cleanliness around the animal. They also ensure that the animal is situated on comfortable bedding suitable for their condition and implement measures to

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prevent self-­injury. Additionally, technicians can make adjustments to room temperature, humidity, and lighting to enhance the animal’s comfort. Furthermore, veterinary technicians assist or guide caregivers in selecting and installing assistive devices in the home environment, such as ramps, gates, and enhanced floor traction, among others. These adaptations help improve the animal’s mobility and overall quality of life during palliative care.

18.2.6  Social Environment Human-­animal interaction and socialization, also known as social resilience, are crucial aspects of maintaining a high quality of life for animals in palliative care. Veterinary technicians play a key role in guiding and motivating caregivers to prioritize spending quality time with the animal to meet these emotional needs. This includes facilitating interactions between the animal and human family members, as well as encouraging positive social interactions with other animals when appropriate. Such engagement contributes significantly to the animal’s overall well-­being during their palliative care journey. They can also help caregivers understand possible dynamic changes between the animals in the home and how to minimize stress in hierarchy changes.

18.2.7  Support for the Family Effective communication with caregivers in veterinary palliative care requires a combination of knowledge, understanding, and sensitivity. It’s crucial to demonstrate empathy for both the animal and the caregiver, acknowledging the emotional bond between them. Active listening plays a vital role in understanding caregivers’ stories and concerns, offering them a valuable outlet during this challenging time. Veterinary staff should recognize the significance of the pet within the family dynamic, validating and normalizing anticipatory grief to

18.2  ­Technicians’ Roles in a Hospice and Palliative Care Practic

help caregivers navigate the grieving process effectively (Lagoni et al. 1994). Drawing from their expertise, veterinary technicians can provide guidance and support caregivers in making difficult decisions. Empowering caregivers with information and resources enables them to navigate the complexities of palliative care more confidently. Moreover, veterinary technicians must be emotionally available and supportive when caregivers need it most, fostering a compassionate and understanding environment.

18.2.8  Pain Recognition and Management As with any other aspect of veterinary care, identifying and easing pain is a fundamental objective in veterinary hospice and palliative care. Effective pain management not only enhances the animal’s quality of life but also alleviates anxiety for caregivers. In this context, one of the key roles of veterinary technicians in hospice and palliative care is to raise caregivers’ awareness regarding the profound impact of pain on the animal’s well-­being. Educating caregivers about how to identify subtle signs of pain in their animals’ behavior falls under the responsibility of veterinary technicians. Continually reinforcing this information and highlighting relevant behaviors when they arise is crucial for ensuring caregiver compliance with pain management strategies. Animals, particularly those enduring chronic pain, can exhibit subtle behavioral changes that might go unnoticed. For a comprehensive understanding of how to recognize pain in companion animals, please refer to Chapter 4. 18.2.8.1  Neoplasia

Neoplasia can impact various organ systems and anatomical locations, including the face, head and neck, thorax, abdomen, limbs, spine, and central nervous system. In humans, a significant percentage (30–­60%) of cancer patients report experiencing pain at the time of diagnosis, with even higher rates (70% or more) in advanced stages of the disease. Specific types of

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tumors can lead to intense pain, such as bone tumors and soft tissue tumors in the oral cavity not originating from the gingiva. Gastrointestinal tumors may cause blockage, ulceration, or distension of the GI tract, while tumors affecting peripheral nerve tissue can result in neuropathic pain that is often challenging to manage. Additionally, invasive and ulcerated skin tumors tend to be painful (Fox 2010). The typical cancer progression involves patients maintaining a relatively high level of functioning until late stages of the disease, at which point there is a sudden and steep decline over a few weeks or even days, ultimately leading to death. Pain can manifest at any stage of the disease, emphasizing the importance of caregivers and healthcare providers being vigilant in observing for signs of pain. Even if obvious signs are not present, considering a therapeutic trial for pain management in tumors known to cause pain is prudent. 18.2.8.2  Osteoarthritis

Osteoarthritis is inherently painful and requires treatment regardless of whether it is the primary diagnosis or a comorbidity alongside another primary condition. In advanced stages of the disease, episodes of prolonged inability to stand up or remain standing without external support may occur, necessitating aggressive interventions to assist with mobility or consideration of euthanasia. If the animal is also recumbent additional pain can be experienced via pressure on arthritic joints. Clinical manifestations of advanced osteoarthritis can sometimes resemble neurological deficits, and these conditions may coexist in some cases. Aggressive multimodal pain therapy and appropriately padded bedding may be necessary to differentiate between the two conditions and assess the patient’s response to treatment. 18.2.8.3  Analgesia for Specific Procedures and Special Problems

The analgesia and anesthesia protocols used for hospice and palliative care patients are similar to those for patients with comparable medical

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conditions and risk factors. However, in ­hospice and palliative care, assessing the balance between risks and benefits takes on a unique significance. Certain long-­term side effects that would typically be considered high risk might be deemed acceptable in hospice care due to its short-­term nature. This delicate balance must be carefully evaluated and discussed with the family when planning various procedures, including diagnostic tests like imaging, biopsies, and specimen collection, as well as treatment procedures such as catheter placement, feeding tubes, physical therapy, wound care, and occasionally palliative surgery. Additionally, the selection of pharmacological agents, including analgesic medications and their routes of administration, as well as nonmedical care such as bathing, grooming, or transportation, should all be carefully considered and explained to the caregivers so they can make informed decisions on behalf of the patient. Educating caregivers about the importance of grooming focuses on alleviating discomfort and promoting the patient’s overall well-­being. It’s also an opportunity for them to provide care, connection, and security to their pets in  this vulnerable time. Minimizing stress by  proceeding calmly, using familiar tools, and adapting to the pet’s pace is essential. Grooming at this stage transcends mere hygiene; it’s a compassionate effort to enhance the pet’s overall comfort, dignity, and connection. The veterinary technician can assist the owner in determining what grooming will be beneficial to the patient while taking into consideration the stress that bathing, professional grooming, or simply transporting the patient may cause.

18.2.9  Advocacy Veterinary technicians play a crucial role as advocates within the hospice team, advocating for both animal patients and their human caregivers, particularly in situations where patients and caregivers feel powerless, vulnerable, or unable to communicate clearly. This

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advocacy becomes especially vital at the end of life (Thacker 2008). In many cases, veterinarians deliver challenging news to pet owners, such as a terminal diagnosis. If the veterinarian’s communication lacks compassion or clarity, veterinary technicians step in as advocates, becoming compassionate communicators and interpreters of information. They can rephrase and explain the information shared during consultations, helping caregivers grasp both the medical details and their own emotions in the given situation. Furthermore, technicians can relay any additional questions or concerns back to the veterinarian. Moreover, veterinary technicians uniquely bridge the communication gap by documenting families’ concerns and emotions in the patient’s care plan and medical records. They also facilitate verbal discussions during shift handoffs and multidisciplinary team rounds, ensuring that the entire veterinary team remains informed and aligned with the caregivers’ needs (Hebert et al. 2011).

18.3  ­Euthanasia and Analgesia for the Dying Patient The veterinary team shifts its focus toward ensuring maximum comfort and peace for both the patient and the family during the final stages of life and the dying process. Euthanasia, which translates to “good death,” involves the intentional termination of life through medical intervention, employing methods that do not cause pain, discomfort, or anxiety. Historically, euthanasia has been a preferred method in mainstream veterinary care for ending the suffering of patients with life-­limiting illnesses. In the context of animal hospice and  palliative care, euthanasia is an accepted option aimed at relieving an animal’s suffering by peacefully and humanely ending life when other means of alleviating suffering have been exhausted or are unavailable. On the other hand, “natural death” refers to the preference of an animal’s caregiver, acting

18.3  ­Euthanasia and Analgesia for the Dying Patien

as the patient’s surrogate, to allow the dying process to unfold comfortably without resorting to euthanasia. Natural death is considered a viable option in animal hospice and palliative care as long as the animal can be maintained in a reasonably comfortable state. Caregivers, serving as the patient’s surrogates, hold the right and responsibility to determine what is in the animal’s best interest. It’s crucial for caregivers and the veterinary team to collaborate effectively in making end-­ of-­life decisions, ensuring that the animal’s well-­being remains the primary focus throughout the process.

18.3.1  Euthanasia The well-­being and comfort of the animal should always be the top priority when considering euthanasia. Opting for euthanasia in the home environment offers several advantages. It eliminates the need to transport a debilitated and potentially painful animal to a clinic setting and provides optimal privacy for the family during this sensitive time. If euthanasia must take place at a clinic, is recommended that clinic staff ensure the family and pet remain together throughout the process. The procedure should be conducted in a comfortable and private room, allowing the family time for reflection both before and after euthanasia. Encouraging caregivers to be present during euthanasia is important. The authors encourage that no animal die alone and recommend a staff member console or hold an animal if there are no caregivers willing to be present. When performed correctly, euthanasia is a painless medical procedure that results in death within minutes. Veterinarians should have a thorough understanding of all approved euthanasia techniques outlined by the American Veterinary Medical Association (AVMA). For dogs, cats, and other small companion animals, the preferred method involves an intravenous injection of a pentobarbital-­ based euthanasia solution through an indwelling IV catheter. However, in cases where

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hospice patients may have compromised physiological functions, knowledge of alternative euthanasia techniques is crucial to ensure a quick and effective response if the primary method cannot be used. Administering sedatives before euthanasia, whenever feasible, is highly recommended and considered standard practice for veterinary patients. For example, a combination of Telazol (2–­4 mg/kg IV) and butorphanol (0.2–­0.4 mg/kg IV) can effectively induce sedation and muscle relaxation in dogs and cats. In cases where an IV catheter is not in place, the same drug combination can be administered intramuscularly or subcutaneously, though there may be mild discomfort or agitation initially before the drugs take full effect. These considerations should be carefully weighed against the potential stress of IV catheter placement or the risk of complications during direct intravenous injection. For detailed information about euthanasia techniques, please read this  2012 book by Dr. Kathleen Cooney and others, Veterinary Euthanasia Techniques: A Practical Guide (Ames, IA: Wiley-­Blackwell), and the 2020 edition of the AVMA Guidelines for the Euthanasia of Animals. While pre-­euthanasia sedation or anesthesia is not required for euthanasia to be humane, the AVMA euthanasia guidelines (AVMA 2020) recommend that pre-­euthanasia sedation or anesthesia be administered to the animal whenever possible. The use of sedation significantly reduces the chances of a stressful experience during euthanasia. Caregivers find comfort in witnessing their companion animal in a tranquil state, free from environmental stressors, as they pass away peacefully. The veterinarian bears the responsibility of evaluating the advantages and potential risks associated with administering pre-­euthanasia sedation or anesthesia. They must carefully consider whether it is beneficial to proceed with euthanasia with or without sedation based on the individual circumstances of the patient. Several other medications can be used, either alone or in combination, before euthanasia.

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Pre-­euthanasia oral sedative examples: ­trazodone (10 mg/kg), gabapentin (20 mg/kg), melatonin (5 mg/kg).

18.3.2  Natural Death Veterinarians and veterinary technicians typically do not undergo formal training in managing the dying process without resorting to euthanasia. Many professionals in the veterinary field have limited exposure to observing animals in their final hours without intervening with life-­saving measures or euthanasia. The insights provided in the following section draw on evidence gathered from human patients who can articulate their experiences during the last hours of life (Emanuel et  al.  2005). Although acquiring direct proof can be challenging, a growing body of scientific research indicates that many mammalian species share sensations, feelings, and emotions akin to those experienced by humans (Balcombe  2006). Therefore, extrapolating from human experiences can offer valuable insights and complement observations of nonverbal communication in animals. The term terminal clinical decline encompasses various physiological changes that occur in the final days, hours, and moments before death. Early signs and changes observed during the initial phase of terminal clinical decline may include restlessness, agitation, difficulty finding comfort, social withdrawal, increased sleepiness or lethargy, and reduced intake of food and water. In the late phase of terminal clinical decline (active dying), significant alterations in respiratory, cardiovascular, renal, and neurological functions commonly manifest. The neurological changes associated with the dying process result from multiple irreversible factors occurring simultaneously. Characteristics such as muscle rigidity, an open mouth, and loss of sensation in the extremities are considered normal. Changes in consciousness may progress from decreasing levels to obtundation, semi-­comatose states, coma, and eventual death. The absence of palpebral reflexes indicates a profound level of

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coma similar to that induced by surgical anesthesia. In a minority of patients, dying may present as terminal delirium, characterized by confusion, anxiety, restlessness, and/or agitation (Emanuel et al. 2005).

18.3.3  Pain Management for the Dying Animal Veterinary technicians play a crucial role in providing care to patients nearing the end of life, often spending more time with these patients than any other member of the veterinary team. As advocates for patient comfort, they are actively involved in assessing and addressing a range of symptoms. Ensuring the management of sensations like pain, respiratory distress, hunger, thirst, and fatigue, as well as addressing feelings of depression, anxiety, and agitation, is vital to facilitating a stress-­free dying process. Pain management at the end of life adheres to general multimodal principles, with nonsteroidal anti-­inflammatory drugs (NSAIDs) and opioid agents forming the core of effective analgesia. Adjuvant drugs are used as necessary to supplement treatment. Drugs like gabapentin (initial dosage 5–­10 mg/kg 2–­4 times a day, with a gradual increase by 50% every 5 days may be required) and amantadine (3–­5 mg/kg once daily, long-­term) can be particularly beneficial for managing severe pain associated with cancer and osteoarthritis. However, determining the appropriate dosages for these medications can be challenging, necessitating frequent assessments using validated pain scoring tools. While potential long-­term adverse effects such as liver failure and drug addiction are of minimal concern, immediate adverse effects impacting patient comfort require prompt reassessment of the treatment plan. Cannabis therapy is an integrative pain control option that many owners may seek out in addition to traditional methods due to its recent popularity for a myriad of medical conditions. Cannabis therapy in veterinary and human medicine has shown evidence of anti-­inflammatory and analgesic properties. Although traditional

18.5 ­Conclusio

pain control with NSAIDs, opioids, and adjuvant drugs like gabapentin and amantadine should be pursued first, integrative approaches like cannabis products or other less-­traditional means may be an appropriate addition to the pain control regimen. Sedation is a common adverse effect of many analgesic agents, especially at higher dosages. Balancing the goal of enhancing patient comfort while minimizing loss of conscious awareness at the end of life poses significant medical and ethical challenges, causing distress for caregivers and animal hospice professionals alike. Administering medications orally to end-­of-­ life patients can be challenging and emotionally taxing for both patients and caregivers. Whenever feasible, utilizing routes such as oral transmucosal, intranasal, transdermal, rectal, or subcutaneous administration is preferred. The intravenous route may be convenient if a catheter is already in place, but oral and intramuscular methods should be reserved as last resorts when no other options are available. Assessing pain in patients who are semiconscious, obtunded, or experiencing delirium can be complex. While caregivers often worry about sudden increases in pain as the patient nears death, there is no conclusive evidence to support this concern (Emanuel et  al.,  2005). However, it is crucial to consider the possibility of pain when observing physiological signs such as transient tachycardia, grimacing, or sustained facial tension. Distinguishing pain from symptoms like restlessness, agitation, moaning, and groaning associated with terminal delirium can be challenging. A positive response to a trial dose of opioids may indicate the presence of pain and guide further pain management decisions.

18.4  ­Support for the Family of the Dying Patient Veterinary technicians play an important role in guiding and supporting caregivers as they navigate the difficult decisions surrounding the death of their pet. This may involve

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discussions about whether, when, or where euthanasia should occur, as well as who should be present during the procedure. Veterinary technicians also provide information about what to expect during the dying process, whether euthanasia is involved or not. It’s important to note that behaviors like moaning, groaning, and grimacing, which often accompany agitation and restlessness in terminal delirium, are commonly misinterpreted as signs of physical pain. This misinterpretation can be distressing for both caregivers and members of the veterinary team. Veterinary technicians can help educate the family about the condition, its irreversible nature, and strategies for managing it. It’s crucial for all observers to understand that what they see may not accurately reflect the patient’s experience. Additionally, veterinary technicians must be knowledgeable about the grieving process and equipped to provide compassionate emotional support to caregivers throughout the entire journey, from before the death of the pet to after. Following up with caregivers post-­loss reinforces the caring nature of the animal hospice team toward both the animal and the caregiver. It’s also beneficial for veterinary technicians to be trained in recognizing behaviors that suggest a caregiver may be experiencing complicated grief, allowing for a referral to a licensed counselor when needed. Again, with the recent addition of veterinary social workers to the field, a consultation with a veterinary social worker prior to a patient’s death and after can be invaluable in supporting the caregiver.

18.5  ­Conclusion Hospice and palliative care offer veterinary technicians unique opportunities to engage in meaningful human-­animal relationships and provide crucial support to caregivers. The insights gained by veterinary technicians are vital for guiding families through difficult decisions in hospice care. Central to hospice and palliative care is the goal of recognizing and

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alleviating pain, a responsibility that underscores the importance of veterinary technicians in increasing caregivers’ awareness of the impact of pain on an animal’s quality of life. Effective pain management in hospice and palliative care involves employing multimodal, interdisciplinary strategies that are relevant regardless of the underlying cause. Managing severe pain necessitates proactive medication administration on a schedule, rather than waiting for pain to escalate. The aim is to achieve optimal pain relief using the lowest effective medication dosages. Veterinary technicians involved in end-­of-­life care must possess a thorough understanding of

the patient’s health status, the caregiver’s care goals, the expected progression of the dying process, and options for managing associated clinical signs. Their role encompasses advocating for both the patient and the caregiver while collaborating with the veterinary team. They ­contribute to care planning, assist in medical procedures, educate caregivers, and offer compassionate emotional support. Furthermore, veterinary technicians play a crucial role in guiding caregivers toward making decisions that minimize regrets, allowing the end-­of-­life caregiving experience to be a meaningful and positive journey for all involved.

­References Adams, C.L., Bonnett, B.N., and Meek, A.H. (2000). Predictors of owner response to companion animal death in 177 clients from 14 practices in Ontario. Journal of the American Veterinary Association 217: 1303–­1309. AVMA (2020). AVMA Guidelines for the Euthanasia of Animals, 2020e. Schaumburg, IL: AVMA. Balcombe, J. (2006). Pleasurable Kingdom. London: MacMillan. Cooney, K.A. (2012). Veterinary Euthanasia Techniques: A Practical Guide. Ames, IA: Wiley-­Blackwell. Emanuel, L.L., Ferris, F.D., von Gunten, C.F. et al. (2005). EPEC-­O: Education in Palliative and End-­of-­Life Care for Oncology. Chicago, IL: EPEC. Fox, S.M. (2010). Chronic Pain in Small Animal Medicine. London: Manson Publishing.

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Hebert, K., Moore, H., and Rooney, J. (2011). The nurse advocate in end-­of-­life care. The Ochsner Journal 11: 325–­329. Lagoni, L., Butler, C., and Hetts, S. (1994). The Human-­Animal Bond and Grief. Philadelphia, PA: Saunders. National Institute on Aging. (2021). What are palliative care and hospice care? https://www. nia.nih.gov/health/what-­are-­palliative-­care-­ and-­hospice-­care (accessed November 27, 2022). Shearer, T.S. (2011). Palliative medicine and hospice care. Veterinary Clinics of North America: Small Animal Practice 41 (3): 477–­702. Thacker, K. (2008). Nurses’ advocacy behaviors in end-­of-­life nursing care. Nursing Ethics 15 (2): 174–­185.

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19 Selected Case Studies in Analgesia Tasha McNerney1,2, Darci Palmer 1,3, and Stephen Niño Cital1,4,5 1

The Veterinary Anesthesia Nerds, LLC., Sheridan, WY, USA Mt. Laurel Animal Hospital, Mt. Laurel, NJ, USA 3 Tuskegee University College of Veterinary Medicine, Tuskegee, AL, USA 4 Howard Hughes Medical Institute at Stanford University, Stanford, CA, USA 5 Remedy Veterinary Specialists, San Francisco, CA, USA 2

For several reasons, learning from analgesia case studies and real-­world examples in veterinary medicine is essential. First, it enhances clinical reasoning skills by allowing veterinary professionals to analyze real cases, identify symptoms, make accurate diagnoses, and develop analgesic treatment plans. This practical application of knowledge improves the ability to make informed decisions in real clinical settings with animal patients. Second, case studies bridge the gap between theoretical knowledge and its practical implementation. They provide a tangible context for us to understand the complexities and nuances of veterinary practice that didactic learning alone may not capture. Furthermore, case studies often present ethical dilemmas and complex decision-­making

processes in veterinary medicine. By examining these real-­l ife scenarios, we can understand the real-­world considerations involved in analgesic care and the importance of evidence-­based medicine when creating an analgesic plan. We then learn to base our decisions on the best available scientific evidence and navigate ethical challenges related to animal welfare, client communication, and treatment choices. Additionally, case studies allow us to practice interdisciplinary collaboration and communication skills within the veterinary team. This allows us to work effectively with veterinary nurses, technicians, and other professionals to develop comprehensive treatment plans for our patients.

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

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Case 19.1  Castration Signalment: Bailey, 6-­month-­old male, Canine-­Chihuahua, 4.2 kg Considerations: Lab values (BUN, creatinine, glucose, electrolytes, PCV/TS) WNL. No abnormalities detected on physical exam. No abnormalities on thoracic auscultation. Mentation is excited and anxious. Anticipated Pain Level: Mild to Moderate, somatic nociception Analgesic/Anesthetic Plan: Premedication with trazodone and gabapentin at home prior to drop off at clinic to minimize stress and anxiety. Intramuscular injection of butorphanol and dexmedetomidine. Once adequately sedated and IV catheter placed, induction with ketamine followed by propofol. Intubation and maintenance with inhalant anesthetic in 100% O2. Intratesticular block with lidocaine infiltration in each testicle and along incision. Subcutaneous (SQ) injection of carprofen. Cryotherapy with a cold pack on incision site ­post-­op. Oral carprofen sent home for 5 days following surgery (or longer based on client communication) Discussion: Bailey was still quite anxious upon arrival despite being given gabapentin and trazodone prior to surgery drop-­off. The decision was made to include the ketamine that would have been given prior to propofol with his butorphanol and dexmedetomidine combination. These three drugs were administered IM and Bailey was allowed to wait in a quiet room with a technician while these drugs took effect. Once the patient was immobile, the technician placed an IV catheter. Propofol was administered IV while O2 was administered via facemask. After intubation Bailey was started on sevoflurane 2% in 100% O2. An intra-­testicular block was performed using lidocaine with 0.3 ml placed in each testicle and 0.3 ml infiltrated subcutaneously along the incision site. Once depth was adequate, sevoflurane was decreased to 1.5% and surgery was initiated. Surgery was performed with no major complications or blood loss. All monitoring parameters were WNL during the surgical procedure which had a total time of 19 minutes. In recovery, SQ injection of carprofen was given and a technician administered a cold pack to the incision site while monitoring. Bailey had an uneventful recovery, however 3 hours post-­op he was given a pain score of 2/4 using the Colorado Pain Scoring sheet. A 0.03 mg/kg dose of buprenorphine was administered OTM.

Case 19.2  Ovariohysterectomy Signalment: Cupcake, 1-­year-­old female, Feline-­Siamese, 3.8 kg. Considerations: Lab values (BUN, creatinine, glucose, electrolytes, PCV/TS) WNL. No abnormalities detected on the physical exam. No abnormalities on thoracic auscultation. Mentation is fearful and anxious. Anticipated Pain Level: Moderate, anticipate both visceral and somatic nociception. Analgesic/Anesthetic Plan: Premedication with trazodone and gabapentin at home prior to drop-­off at clinic to minimize stress and anxiety. Intramuscular injection of methadone and dexmedetomidine. Once adequately sedated and IV catheter placed, induction with ketamine followed by propofol. She was intubated and maintained on isoflurane in 100% O2. Intraperitoneal lavage with bupivacaine/saline mixture prior to surgical closure. Liposomal encapsulated bupivacaine in layers of closure. SQ injection of robenacoxib. Cryotherapy with

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19  Selected Case Studies in Analgesia

a cold pack on incision site post-­op. A 5-­ day treatment of oral robenacoxib and OTM buprenorphine was sent home following surgery (longer treatment is possible, based on client communication). Discussion: Cupcake was calm and curious upon arrival and intake. She was given gabapentin and trazodone approximately 1 hour prior to surgery drop-­off. Instead of bringing her to the back and exposing her to a more stressful scenario, the methadone and dexmedetomidine combination was given in the exam room. These drugs were administered IM and Cupcake was allowed to wait in the exam room with a technician while these drugs took effect. Once at an adequate plane of sedation, the technician placed an IV catheter. Ketamine (1 mg/kg) was administered followed by propofol IV while O2 was administered via facemask. She was intubated and maintained on sevoflurane 2% in 100% O2. Once depth was adequate, surgery was initiated. Surgery was performed with no major complications or blood loss. Prior to closure, the surgeon performed an intraperitoneal lavage using bupivacaine diluted with saline. All monitoring parameters were WNL during the anesthetic procedure which had a total time of 26 minutes. Liposomal encapsulated bupivacaine was placed in the layers of closure. In recovery, SQ injection of robenacoxib was given and a technician administered a cold pack to the incision site while monitoring. Cupcake had an uneventful recovery and continued to receive OTM buprenorphine every 8 hours through the evening. She did not require additional analgesics that evening based on the feline grimace scale. She was discharged the next morning with OTM buprenorphine and robenacoxib.

Case 19.3  Dentistry with Multiple Extractions Signalment: Lucy, 10-­year-­old female, Canine-­Poodle Mix, 8.5 kg. Considerations: III/VI heart murmur on thoracic auscultation. Owner declined echocardiography. Lab values on chemistry (BUN, creatinine, glucose, electrolytes) WNL. CBC shows neutrophilia and normal PCV/TS. No abnormalities on abdominal palpation. Mentation is anxious, she would not allow an awake ECG. Anticipated Pain Level: Moderate, anticipate mostly somatic nociception with possible neuropathic component. Analgesic/Anesthetic Plan: Premedication with gabapentin at home prior to dropping off at the clinic to minimize stress and anxiety. Intramuscular injection of methadone and midazolam. Once adequately sedated and IV catheter placed, induction with alfaxalone. Intubation and maintenance on sevoflurane in 100% O2. Dental blocks with ropivacaine based on possible extractions. SQ injection of meloxicam. Low-­level laser therapy (LLLT) to reduce inflammation of oral surgery site post-­op. Oral meloxicam sent home with owner for 5 days following surgery (or longer based on client communication). Will possibly also go home with gabapentin and OTM buprenorphine depending on the number of extractions. Discussion: Lucy was fairly calm when she was dropped off for dentistry. She allowed IV catheter placement without additional medications. IV premedication with methadone and midazolam was initiated while administering O2 via flow by mask. Induction with alfaxalone and intubation was achieved without complication. Maintenance of anesthesia with isoflurane in 100% O2. After dental cleaning, charting, and radiographs it was determined 11 teeth met the requirement for extraction. As these extractions occupied multiple quadrants, maxillary and mandibular dental blocks using ropivacaine were performed bilaterally,

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specifically the caudal maxillary block and the caudal inferior alveolar block. Oral surgery was performed without complication. Most parameters were WNL during the anesthetic procedure, which had a total time of 136 minutes. Lucy did experience some bradycardia which was responsive to glycopyrrolate. Before discontinuing anesthesia, a low-­level laser on the inflammation setting was used on any oral surgery sites. Lucy was given a SQ injection of meloxicam, and her recovery was uneventful. She went home with 3 days of oral meloxicam and 10 days of gabapentin.

Case 19.4  Tibial Plateau Leveling Osteotomy Signalment: Rocky, 3-­year-­old castrated male, Canine – American Bulldog Mix, 36 kg. Considerations: Lab values on chemistry (BUN, creatinine, glucose, electrolytes) WNL. PCV/TS WNL. No abnormalities on abdominal palpation or chest auscultation. Mentation is calm. Anticipated Pain Level: Moderate, anticipate mostly somatic nociception. Analgesic/Anesthetic Plan: Premedication with gabapentin/trazodone/oral maropitant at home prior to dropping off at the clinic to minimize stress and anxiety. Intramuscular injection of methadone & dexmedetomidine. Once adequately sedated, an IV catheter was placed; induction with ketamine followed by alfaxalone. He was intubated and maintained on isoflurane in 100% O2. Ultrasound-­guided femoral and sciatic nerve blocks using bupivacaine with dexmedetomidine added to extend the duration of action. Liposomal encapsulated bupivacaine during surgical closure. Cryotherapy was used on the incision site after surgery for at least 20 minutes. Subcutaneous injection of carprofen. Oral carprofen was sent home with owner for 5 days following surgery (or longer based on client communication). Will possibly also go home with gabapentin and acetaminophen with codeine. Discussion: Rocky was fairly calm when he was dropped off for surgery. He allowed IV catheter placement without additional medications. IV premedication with hydromorphone and dexmedetomidine was initiated while administering O2 via flow by mask. Induction was performed with ketamine followed by alfaxalone, and intubation was achieved without complication. Maintenance of anesthesia with isoflurane in 100% O2. After planning radiographs, ultrasound-­guided femoral and sciatic blocks were applied using bupivacaine with dexmedetomidine. Surgery was performed without complication. Most parameters were WNL during the anesthetic procedure which had a total time of 112 minutes. Rocky did experience some hypotension, which was responsive to decreasing inhalant anesthesia. Rocky did react to some surgical stimulation, and a small dose of ketamine was given IV to provide additional analgesia. Liposomal encapsulated bupivacaine was placed in the layers of closure for extended analgesia. Rocky was given a SQ injection of carprofen as well as a cold compress of his stifle and his recovery was uneventful. Rocky was placed on intermittent doses of hydromorphone every 6 hours based on pain scoring using the Colorado Acute Pain Scale. He went home with 3 days of oral carprofen and 5 days of acetaminophen with codeine. Owners were also instructed to do a cold compress every 8 hours for at least 20 minutes each session. Rocky was set up with an appointment with the rehabilitation team for a post-­surgical evaluation.

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19  Selected Case Studies in Analgesia

Case 19.5  Splenectomy Signalment: Ash, 13-­year-­old castrated male, Shih Tzu mix, 8.9 kg. Presented with a 2-­day ­history of lethargy and straining to defecate. Considerations: Abdominal palpation revealed a hard swelling and abdominal radiographs revealed a potential mass. CT showed the mass associated with the spleen. An exploratory laparotomy revealed a large hematoma on the spleen resulting in a splenectomy. No other masses were identified. CBC/CHEM was unremarkable. Anticipated Pain Level: Moderate with both somatic and visceral nociception Analgesia/Anesthesia Plan: An IV catheter was placed prior to drug administration. Premedication consisted of dexmedetomidine, hydromorphone and maropitant. Induction consisted of ketamine and alfaxalone titrated to effect. Patient was intubated and placed on isoflurane in 100% oxygen. A loading dosage of lidocaine and lidocaine CRI was started intra-­op. A TAP block was performed prior to surgery. He went home with 3 days of oral carprofen and 5 days of acetaminophen with codeine. Owners were also instructed to do a cold compress every 8 hours for at least 20 minutes each session. Discussion: Ash was calm and quite on presentation, so an IV catheter was placed before drug administration. A low dosage (2 mcg/kg) of dexmedetomidine and hydromorphone was given IV. The dexmedetomidine provided moderate sedation and analgesia, which allowed a lower dosage of alfaxalone to be used for induction and a lower inhalant concentration from the start of anesthesia. Administration of maropitant preoperatively helped minimize postoperative nausea, so Ash was interested in small amounts of soft food the evening of the surgical procedure. The lidocaine CRI was utilized for added visceral analgesia. Intra-­operative nociceptive stimulation was addressed with an additional dose of hydromorphone. Recovery was smooth and uneventful.

Case 19.6  Lateral Thoracotomy Signalment: Taki, 6-­month-­old male, Pitbull mix, 4 kg. Presented with recurrent regurgitation and failure to thrive with a BCS 2/9. Considerations: Thoracic radiographs and barium study confirmed the presence of a persistent right aortic arch (PRAA). CBC/CHEM was unremarkable. A lateral thoracotomy was performed between the fourth and fifth intercostal spaces. A chest tube was placed intra-­operative and left in place for 24 hours. Anticipated Pain Level: moderate-­severe somatic and visceral nociception Analgesia/Anesthesia Plan: Gabapentin oral solution was administered the night before surgery to help minimize stress of hospitalization. Premedication consisted of hydromorphone IM, and maropitant IV once a catheter was placed. Ketamine, midazolam, and propofol were used for induction. Maintenance consisted of isoflurane in 100% oxygen. Intercostal nerve blocks performed with bupivacaine prior to surgical incision. Intraoperative nociceptive stimulation was addressed with micro doses of dexmedetomidine. Injectable meloxicam was administered SQ postoperatively. Hydromorphone (0.1 mg/kg) was administered IV postoperative. Meloxicam oral suspension was administered once a day for 7 days, acetaminophen tablets

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10 mg/kg two to three times a day, and gabapentin oral suspension twice a day for 10 days were sent home. Discussion: A sub-­anesthetic dosage of ketamine was added to the induction protocol for its NMDA antagonist activity. Due to the overlapping nerve supply in the thoracic region, intercostal nerve blocks were performed with bupivacaine two intercostal spaces cranially and two intercostal spaces caudal to the incision. A microdosage (1 mcg/kg) of dexmedetomidine was administered intraoperative due to an increase in heart rate and blood pressure that occurred with the initial incision. The combination of hydromorphone, ketamine, bupivacaine, and dexmedetomidine provided excellent multimodal analgesia so that the inhalant concentration could be kept low. Anesthetic depth remained adequate throughout the procedure. Meloxicam was administered SQ postoperative and was sent home in oral formulation with the owner. Gabapentin was sent home to help provide mild sedation during the initial recovery phase. Hydromorphone was re-­dosed twice during the first 24 hours after surgery. The decision to re-­ dose was based on pain scores and the timing of the last dose to ensure that more than 6 hours did not lapse between doses. Orders were written to instill bupivacaine into the chest tube if Taki became acutely painful in recovery, but he never appeared uncomfortable enough to initiate this treatment.

Case 19.7  Hemilaminectomy Signalment: Pandora, 6-­year-­old spayed female, Stafford Terrier Considerations: Patient started to show signs of hindlimb paresis 2 weeks prior to presentation. She was cage rested and received three treatments of cold laser therapy. One day before presentation, Pandora attempted to stand up and immediately started vocalizing and was unable to walk. This is the third IVDD incident for this patient. The first event resolved on its own with cage rest. The second event occurred 1 year and 2 months ago and resulted in hindlimb paraplegia and incontinence, but deep pain was present. A hemilaminectomy was performed at L2–L3. Recovery was uneventful and Pandora regained mobility within 3 weeks of the procedure. The owners remained vigilant with physical therapy doing daily passive range of motion in all limbs and swimming two to three times a week. On presentation for this third incident, she was bright, alert, and responsive. The rDVM prescribed prednisone, gabapentin, methocarbamol, and buprenorphine. MRI were consistent with a right-­sided lesion at L4–L5, so a hemilaminectomy was performed. CBC was WNL. Chemistry revealed hypoglycemia, slightly elevated ALT, and significant elevation of ALP. Anticipated Pain Level: moderate to severe; somatic nociception with a neuropathic component. Analgesia/Anesthesia Plan: Gabapentin was administered orally the morning of the surgical procedure. An IV catheter was placed prior to drug administration. Premedication consisted of dexmedetomidine (5 mcg/kg) and buprenorphine (0.04 mg/kg) IV. A combination of ketamine and propofol were utilized for induction. Patient was intubated and placed on isoflurane in 100% oxygen. Intraoperative nociceptive stimulation was managed with a ketamine CRI and dexmedetomidine boluses as needed. Nocita® was used for closure of the surgical site. Prednisone, gabapentin and methocarbamol were continued orally for 14 days. An additional dose of buprenorphine was administered 6 hours post-op due to a Glasgow pain score of 4/20.

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19  Selected Case Studies in Analgesia

Discussion: The chronicity of this condition led clinicians to be suspicious of myelomalacia, which holds a poor prognosis overall. The owners decided to proceed with this second surgical procedure as a way to provide comfort to Pandora during this acute period. The combination of dexmedetomidine and buprenorphine provided excellent sedation and analgesia preoperatively. The dosage of buprenorphine provided comparable somatic analgesia to the agonist opioids with the added advantage of having a long duration of action and minimal adverse effects. Induction and intubation were uneventful. A sub-­anesthetic dosage of ketamine was used in combination with the propofol to help decrease the propofol dose required for intubation and to serve as loading dose for the ketamine CRI. A ketamine CRI was started intraoperative and continued for 24 hours postoperative. Utilizing an NMDA antagonist helped to minimize central sensitization and also helped to provide a “pain vacation” to reset the way the central nervous system responds to chronic pain. Nociceptive stimulation occurred once ­during the initial approach and once at closing so a 1 mcg/kg dexmedetomidine bolus was administered. Nocita® was used as the blocking agent but could have been replaced with regular bupivacaine. Prednisone was gradually tapered down during the 14-­day postoperative period. Gabapentin and methocarbamol were continued for sedation and muscle relaxation during the recovery period.

Case 19.8  Limb Amputation Signalment: Mason, 9-­year-­old castrated male, Australian cattle dog cross. He has a history of aggressive behavior at the veterinary hospital during restraint. Presented with hard swelling of the right front carpus. Radiographs revealed bony destruction of the distal carpus with osteosarcoma highly suspected. Considerations: FNA revealed the presence of neoplastic cells, thoracic CT confirmed negative metastasis. CBC/CHEM was unremarkable. A right front limb amputation was performed. Anticipated Pain Level: Moderate to significant somatic nociception Analgesia/Anesthesia Plan: Mason was sent home with trazodone and gabapentin. The owner administered the drugs the night before and the day of the surgical procedure. Mason was muzzled by his owner before coming into the hospital. He was premedicated with dexmedetomidine (8 mcg/kg) and methadone (0.5 mg/kg) IM. Once sedation was achieved, an IV catheter was placed and maropitant was administered IV. He was induced with ketamine and midazolam, intubated, and placed on isoflurane in 100% oxygen. Carprofen was administered SQ. Intra-­operative bupivacaine was placed intra-­neural prior to ligation of the brachial plexus nerves. Intra-­operative nociceptive stimulation was managed with low-­dose dexmedetomidine IV. An infiltrative, incisional-­line block with bupivacaine was performed after closure was complete. Postoperatively, an additional dose of methadone was administered IV and a fentanyl patch was placed. Carprofen and gabapentin were prescribed for 14 days post-­op. Discussion: The pre-­hospital pharmaceuticals worked well to sedate Mason prior to him coming to the hospital. Premedication and induction were uneventful. A brachial plexus block or RUMM block could be performed, but they will not adequately block the entire forelimb so intra-­neural bupivacaine was administered prior to ligating the larger nerves. Mason’s depth remained adequate throughout the anesthetic event. At one point, his respiratory rate and heart rate increased in response to surgical manipulation. A micro dosage

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19  Selected Case Studies in Analgesia

(1 mcg/kg) of dexmedetomidine was administered IV as treatment. The maximum dosage of bupivacaine was calculated and drawn up for the intra-­neural blocks performed intraoperative. The left over volume was administered as an infiltrative incisional block along the incision after closure. At extubation, Mason was mildly vocal, so an additional dose of methadone was administered IV. He was monitored throughout the night and pain scored to determine if additional doses of methadone were necessary. Mason did not require any further analgesic intervention for 24 hours postoperatively. The fentanyl patch will provide 72 hours of analgesia while the carprofen and gabapentin will be used for postoperative analgesia for 14 days.

Case 19.9  Craniotomy Signalment: Gambee, 10-­year-­old spayed female, Main Coon presented with dull mentation and intermittent circling behavior over the course of several months. One week ago, the owners witnessed a seizure and made an appointment to see a neurologist. Considerations: Neurological exam was consistent with signs of a forebrain lesion, which was suspected to be a meningioma. Owners consented to MRI and surgery. Increased intracranial pressure suspected due to elevated preoperative systolic blood pressure of 150 mmHg and heart rate 100 bpm. Anticipated Pain Level: moderate to severe somatic nociception with a neurological component Analgesia/Anesthesia Plan: Oral gabapentin was administered prior to anesthesia, as well as a loading dose of levetiracetam. An IV catheter was placed prior to any drug administration. Gambee was premedicated IV with midazolam and remifentanil and induced with ketamine and alfaxalone. A remifentanil CRI was started after Gambee was intubated and placed on isoflurane in 100% oxygen for maintenance. A frontal block was performed using ropivacaine and dexmedetomidine for the transfrontal approach. A ketamine CRI was utilized in conjunction with the remifentanil to minimize intra-­ operative nociceptive stimulation. Injectable robenacoxib was administered SQ postoperative and continued orally for an additional 2 days. Discussion: Even though Gambee’s mentation was dull, she still resisted restraint for IV catheter placement. Oral gabapentin was administered and she was left undisturbed for 2 hours. Midazolam and remifentanil provided adequate sedation prior to induction with ketamine and alfaxalone. The sub-­anesthetic dosage of ketamine (0.5 mg/kg) helped to decrease the alfaxalone dose needed for intubation and also served as a loading dose for the ketamine CRI. A bilateral frontal block was performed since the surgeon was using the transfrontal approach to access the tumor. The addition of the local block with ropivacaine helped to eliminate intra-­operative nociceptive stimulation, which allowed the ketamine CRI and remifentanil CRI to be maintained at their starting dosages with no boluses required. Injectable robenacoxib was utilized for inflammatory pain and was administered once a day for 3 days. Gambee was sent home with prednisolone, and OTM buprenorphine as needed.

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19  Selected Case Studies in Analgesia

Case 19.10  Enucleation Due to Trauma Signalment: Panther, 5-­week-­old, 0.5 kg, male DSH presented with a proptosed left eye with a large corneal laceration due to unknown trauma. His calm mentation and reluctance to eat at regular intervals was attributed to pain. Considerations: Pediatric patients are prone to hypothermia due to immature thermoregulation and hypoglycemia when they are not eating at regular intervals. Their hepatic and renal systems are immature. Low drug dosages were utilized to account for decreased metabolism and excretion from the body. Nonsteroidal anti-­inflammatory drugs (NSAIDs) are contraindicated due to the concern for renal damage when the kidneys are not fully functioning. Anticipated Pain Level: moderate to severe somatic nociception Analgesic/Anesthetic Plan: dexmedetomidine, buprenorphine, and ketamine were administered as one IM injection. Intubation occurred once Panther was immobilized. An IV catheter was placed in the medial saphenous vein. Maropitant was administered IV. A retrobulbar block was performed with bupivacaine prior to the start of the surgical procedure. Discussion: Panther was fed a small amount of soft food 1 hour prior to the IM injection to help minimize hypoglycemia. All drugs were diluted to a concentration that allowed for an accurate volume to be drawn up and administered as an IM injection. Dexmedetomidine (2 mcg/kg) and buprenorphine (0.03 mg/kg) provided adequate sedation and analgesia for this procedure. Ketamine (5 mg/kg) served as the induction agent but also as an adjunct analgesic providing NMDA antagonism. Bradycardia was not observed with this drug combination. Anecdotally, there is speculation that pediatric patients do not have an abundance of peripheral alpha-­2 receptors as the dramatic increase in blood pressure and subsequent drop in heart rate and cardiac output seen in adults is not seen in this population of animals. Low-­dose dexmedetomidine can help reduce the MAC of inhalant while providing sedation and analgesia to pediatric patients. Panther was immediately placed on a heat source after the IM injection. Immobilization occurred within 3 minutes. He was intubated and placed on isoflurane in 100% oxygen. Once a catheter was placed, maropitant was administered IV. Maropitant was utilized to help minimize postoperative nausea. Blood glucose was 102 g/dl so supplemental dextrose was not provided. A retrobulbar block was performed with bupivacaine. As an alternative, bupivacaine can be splashed into the orbit once the eye is removed but care must be taken to not soak up the bupivacaine with gauze after placement. The procedure lasted 20 minutes and extubation occurred within 5 minutes of turning off the vaporizer. His postoperative temperature was 101.4 ºF. Panther recovered smoothly and no further analgesia or sedation was needed immediately after extubation. Postoperative glucose was 98 g/dl and he was eager to eat some soft food once he was sitting sternal. His feline grimace score remained less than 2 at all time points throughout the night. Panther was sent home with OTM buprenorphine for 5–7 days.

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Case 19.11  Chronic OA Pain – Canine Signalment: Ducky, is a 11-­year-­old male castrated canine – Springer Spaniel Diagnosis: Osteoarthritis of the rear stifles and hip joints. A comprehensive assessment encompassing joint palpation, range of motion evaluation, and radiographic imaging, with a focus on hip, stifle, and elbow joints was conducted to confirm the diagnosis and gauge the extent of osteoarthritis. The initial therapeutic measures involved implementing weight management strategies to alleviate joint stress, controlled exercise regimens, and provision of orthopedic bedding for enhanced comfort. Discussion of Analgesic Regimen NSAIDs: NSAIDs, specifically carprofen, were prescribed to mitigate pain and reduce inflammation. Concurrent monitoring of hepatic and renal function commenced to preemptively address potential adverse effects, with dosage adjustments made based on the patient’s response and laboratory findings. Polysulfated glycosaminoglycan (Adequan®) was started. Joint supplements containing omega-­3 fatty acids and CBD were introduced to augment joint health and impede the progression of osteoarthritis. These supplements acted as chondroprotective agents, contributing to the preservation of cartilage integrity. Nonpharmacological interventions, namely heat therapy and massage, were recommended to address stiffness and enhance joint flexibility. The application of warm compresses facilitated improved blood circulation, while massage promoted muscle relaxation. The owners agreed to perform heat and massage therapy at least twice weekly. Follow-­Up Assessments: Regular follow-­up assessments were scheduled to monitor Ducky’s clinical progression. These evaluations encompassed joint mobility, pain intensity, and potential adverse effects of medications. Ducky’s owners regularly sent videos showing Ducky on walks and attempting the back porch stairs. Therapeutic adjustments were implemented based on the evolving severity of osteoarthritis and Ducky’s response. Breakthrough Pain and Therapeutic Adjustments: During a subsequent follow-­up, Ducky displayed signs of breakthrough pain, despite the ongoing multimodal therapy. Increased lameness and discomfort prompted a reassessment of the treatment plan. In response to this observed breakthrough pain, a 30-­day course of amantadine was initiated to address the inadequacy of the existing pain management protocol. Amantadine, with its N-­methyl-­D-­aspartate (NMDA) receptor-­modulating properties, was introduced to provide a more robust analgesic effect. Monitoring and Follow-­Up: Close monitoring of Ducky’s response to the adjusted treatment plan is paramount. Follow-­up appointments will involve assessments of pain levels, joint functionality, and potential side effects. Adjustments to the medication regimen will be considered based on the evolving clinical picture.

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19  Selected Case Studies in Analgesia

Case 19.12  Chronic OA Pain – Feline Signalment: Leo, 14-­year-­old, male castrated, feline DLH, 7.1 kg. Presented due to having trouble jumping up onto the bed and had fallen off the couch recently. Considerations: Lab values on chemistry: increased BUN, increased creatinine, normal glucose, normal electrolytes. PCV/TS WNL. No abnormalities on abdominal palpation or chest auscultation. Mentation is fearful and does not like to be brought into the veterinary clinic. Owner has a hard time placing him in the carrier. He is currently on a prescription diet for kidney disease and his owner (human nurse) administers SQ fluids at home (100 ml every other day). He also receives a glucosamine/fatty acid supplement once daily. Anticipated Pain Level: Moderate chronic pain – may have some elements of wind-­up and neuropathic pain. Analgesic/Anesthetic Plan: Due to increased kidney levels we will be avoiding long-­term NSAID use. After the initial consult, the owner is interested in trying CBD for OA inflammation pain. Liquid hemp oil product was dosed every 12 hours and Leo was also given his first polysulfated glycosaminoglycan (PSGAG) (Adequan®) injection. The decision was made to continue SQ injections of PSGAG twice a week for the first 4 weeks and then reevaluate. Also sent home with gabapentin liquid and instructed to give 100 mg 1 hour prior to the car ride on vet visit days. Also recommended weight loss and diet plan. Follow-­up Day 14: After 2 weeks Leo’s owner noted it was too stressful getting him into the carrier and to the vet office for PSGAG injections. Discussed switching to frunevetmab injection once monthly. The owner agreed and has scheduled an appointment with our home-­visit veterinarian. Follow-­up Day 40: The owner was on vacation and unable to check in at the 30-­day mark, however after speaking with her, she noted Leo is now jumping up onto the couch and appears to be chasing objects like the laser pointer again, increasing his play behavior. Owner will continue frunevetmab injections and follow up with a home visit veterinarian. The owner notes home visits are much less stressful for him compared to coming into the hospital.

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Index Note: Page numbers in italics refer to Figures; those in bold to Tables

a

AAEP Lameness Grading System  77 AAHA Pain Management Guidelines Certificate Course  11 Abdomen and Thorax, Regional and Local Blocks of the  144 Absorption  95 Acepromazine  119 Acetaminophen  116, 200, 265, 483 Activity Monitors  54 Acupuncture  1, 13, 488, 489 Acute Lameness  297 Acute Pain Canine  56 Feline  57, 61 General  32, 33, 179, 181, 185, 200, 243, 480 Adaptive Pain  32, 33 Adequan  397 Adjunctive Agents  129 Adjunctive Analgesics  366, 371 Adjunctive Therapies in Zoo Animals  388 Adverse Drug Effects  96 Advocacy  512

Affinity  95 Aging and Disability  457 Aging Patient  427 Agitation  51 Agonist/Antagonist Opioids  105 Alfentanil  100 Allergies, Skin Disease  204 Allosteric binding site  95 Alpha‐­2 Adrenergic Agonists  112, 200, 221, 229, 282, 290, 293, 307, 318, 327, 334, 339 Alpha‐­2 Antagonists  113 Amantadine  115 Amino‐­amides  110 Amino‐­esters  110 Amphibians and Fish  84, 371, 373 Normal Appearance  84 Pain Score  84 Amputation Forelimb  196, 197 Hindlimb  197, 198 Analgesia Specific Uses Castration  167, 168 Dehorning  322 Dying Patient/Euthanasia  512

Exotic Companion Animals  348 Foals  302–­304 Food and Fiber Species  315 Specific Procedures/Special Problems  511 Types Avian  359 Equine  289 Local/Regional  244 Multimodal  15, 179, 180, 234, 277, 323, 331, 332, 336, 340, 341, 359 Reptile  367 Analgesic Adjunct  95 Analgesic Drug  95 Analgesic Pharmacology  95 Analgesics, Adjunctive  366, 371 Analgesics and Techniques in Horses, Locoregional  294 Analgesics, Common (Avian)  363, 365 Analgesics, Common (Rodents)  356, 357 Analgesics, Commonly Used (ER and ICU Patients)  235–­238

Pain Management for Veterinary Technicians and Nurses, Second Edition. Edited by Stephen Niño Cital, Tasha McNerney, and Darci Palmer. © 2025 John Wiley & Sons, Inc. Published 2025 by John Wiley & Sons, Inc. Companion website: www.wiley.com/go/mcnerney/2e 本书版权归John Wiley & Sons Inc.所有

530

Index

b

Bedinvetmab (Librela)  117 Behavior, Pain Amphibians and Fish (Normal)  84 Birds (Normal)  78 Camelids  71 Cattle  63, 71 Companion Animals  59 Horses  74 Rabbits  349, 350 Reptiles (Normal)  82 Rodents  353 Small Exotic Mammals  85 Small Ruminants  71 Swine  73 Bioavailability  95 Biomarkers, Pain  53 Biotransformation  95 Bisphosphonates  116, 270 Blocks Auricular  142 Auriculopalpebral Nerve  138, 140 Auriculotemporal  142 Brachial Plexus  164, 165 Caudal Epidural (Horse)  167, 168 Caudal Epidural (Livestock)  171–­173 Caudal Epidural (Sheep and Goats)  329 Circumferential  144 Common Regional and Local Anesthetic Techniques  143 Cornual (Cattle)  170 Cornual (Sheep and Goats)  327 Cornual Nerve  170, 172 Dental and Facial Regional/ Local Anesthesia  133 Dentistry and Facial Blocking Techniques  133 Epidural  149–­152, 222 Erector Spinae Plane (ESP)  156

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Femoral‐­Saphenous Nerve Complex  160, 161 Frontal Nerve (Supraorbital Foramen)  140, 141 Incisional Line  143, 144, 222 Inferior (Caudal) Alveolar Nerve  133, 200 Infraorbital Nerve  136, 137 Intercostal  144, 145 Interpleural  146 Intratesticular (Sheep and Goats)  330 Intratesticular and Spermatic Cord  147 Intravenous Regional Anesthesia (IVRA) in Cattle  320 Limb  160 Local/Regional  127, 222, 229, 244, 352, 358, 366, 369, 401 Lumbosacral Epidural (Swine)  334 Major Palatine (Small Animal)  137, 138 Middle Mental Foramen Nerve  135, 136 Nerve (Cattle)  318 Paravertebral Nerve (Sheep and Goats)  328 Radial, Ulnar, Median, and Musculocutaneous (RUMM) Nerve  166 Regional and Local Anesthesia (Sheep and Goats)  327 Retrobulbar  140, 141 Sacrococcygeal  147–­148 of the Thorax and Abdomen, Regional and Local  144

c Camelids  335, 337–­342 Canine Acute Pain Scoring  56 Breed or Species Bias  50

Brief Pain Inventory  56 Castration (Pain Management Protocol Example)  518 Chronic Pain Scoring  56 Rehabilitation Veterinary Technician Certifications  12 Cannabis Therapy  514 Carfentanil  100 Carprofen  107 Catastrophizing  29, 30 Cat‐­Friendly Certificate Program  13 Cattle  317–­325 Analgesia for Dehorning  322 Common Painful Surgeries  320 Continuous Infusion Analgesia (CIA)  322 Intravenous Regional Anesthesia (IVRA)  320 Multimodal Analgesia  323 Nerve Blocks  318 Nociceptive Pathway  319 Pain Severity  317 Reasons for Lack of Analgesia  320 Regional Anesthesia and Analgesia Techniques  319 Teat Block  321 Infusion of the Teat Cistern  321 Withdrawal Period  324, 325 Caudal Epidural in a Horse  167, 168 for Livestock  171–­173 Caudal Maxillary Block  138, 139, 200 Central Sensitization  24, 31, 33, 36 Certified Animal Pain Practitioner (CAPP)  10

Index

Certified Companion Animal Rehabilitation Therapist (CCAT)  14 Certified Equine Massage Therapist  12 Certified Veterinary Pain Practitioner (CVPP)  6, 9 Cesarean Section (C‐­Section)  217, 224–­227 Case Management  224, 225 Protocols  226, 227 Chiari Malformation  258 Chinese Acupuncture  1 Chloroprocaine  110 Chronic  33, 34 Pain  253–­272 OA–­Canine (Pain Management Protocol Example)  526 OA–­Feline (Pain Management Protocol Example)  527 Pain Assessment  260 Wounds  259 Cincinnati Orthopedic Disability Index  62 Circumferential Block  144 Client‐­Specific Outcome Measures‐­Feline  58 Clinical Pain Scoring Tools (Canine and Feline)  55 Cocaine  110 Codeine  101 Cognitive Perception Modulation  486 Common Painful Conditions Camelids  338, 342 Cattle  320 Donkeys  304 ER/ICU Setting  246 Sheep and Goats  326, 328 Complete and Balanced Nutrition  467 Complex Regional Pain Syndrome  35

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Concentration  95 Congenital Conditions  454, 455 Continuous Rate Infusion (CRI)  95 Camelids  339 Sheep and Goats  330, 331 Swine  335 Conversion Electron Therapy  441 Cornual Nerve Block  170, 172 Corticosteroids  109, 266, 440 Cranial Disease, Injury or Neurosurgery  193, 194 Craniotomy (Pain Management Protocol Example)  524 Critically Ill and Hospitalized  457 CSU Canine Acute Pain Scale  70 Cutaneous Burns  207–­210 Discomfort  202

Dimethylsulfoxide (DMSO)  294 Dipyrone (Metamizole)  117 Disability and Aging  457 Scoring and Assessment  420 Discomfort (Cutaneous)  202 Disposition and Personality  48 Dissociative Agents  222 Distribution  96 Domains (Pain)  48 Dorsal Horn  18–­27, 33 Dosage  96 Dose  96 Dosing  487 Drugs Analgesic  96 for CRIs  186 Delivery  362 Effects (Adverse)  96 Used for Epidurals  155 Dysfunctional Pain  255 Dysphoria  51 Dystocia  301

d

e

Dehorning (Cattle)  322 Delivery of Care  509 Dental and Facial Regional/ Local Anesthesia  133 Dentistry and Facial Blocking Techniques  133 with Multiple Extractions (Pain Management Protocol Example)  519–­520 Dermatologic Conditions  201 Descending Pathways  23, 27 Detomidine  112 Dexmedetomidine  112, 367 Diagnosis (Veterinary)  418 Diet‐­Related Component (Nutrition Assessment)  466 Diets (Nutrient‐­Focused) 471

Ear Surgery  189 EFCV  96, 99 Electrical Stimulation  434 Electro‐­Magnetic Therapy  436 Elephants  389, 394–­398 Adequan  397 Butorphanol  398 Etorphine  396 Gabapentin  397 NSAIDs  397 Pain Interpretation  394 Pain Queues  395 Pain Treatment  395, 397 Tramadol  398 Vocalizations and Trunk Activity  397 Emergence Agitation  51 Emotional Support  508, 515, 516 Endocannabinoid Axis  41

531

532

Index

Endocannabinoidome (eCBome)  475 Endocannabinoids  23, 27, 476 Endocannabinoid System (ECS)  475 End‐­of‐­Life Care  508, 516 Enucleation (Pain Management Protocol Example)  525 Environmental Management Exotic Companion Animals  350 Physical Rehabilitation  430 Environmental Modifications  272 Epidural  149–­152, 321 Catheter  152–­154 Commonly Used Drugs  155 in a Horse  167, 168 for Livestock  171, 172, 173 Sheep and Goats  329 Equid  73, 79 Equine Analgesia  289 Lameness Grading System  77 Pain Assessment  289 Rehabilitation Veterinary Technician Certifications  12 Erector Spinae Plane (ESP) Block  156 Etodolac  107 Etorphine  396 Euthanasia  512, 513 Evaluating Pain in ER and ICU Patients  234 Excretion  96 Exercises for Early Rehabilitation  453, 454 Exotic Animal Formulary  390–­393 Companion Animals  347, 348 Species  77, 85, 86 Ungulates  402

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Extracorporeal Shock Wave Therapy (ESWT)  435 Eye Surgery  188

f

Facial Blocking Techniques  133 Regional/Local Anesthesia  133 Fear Anxiety, and Stress (FAS)  180 Free Certification  13 Feline Acute Pain Scoring  57 Chronic Pain Scoring  58 Client‐­Specific Outcome Measures  58 Clinical Pain Scoring Tools  55 Grimace Scale  57, 66–­69 Lower Urinary Tract Obstruction  247 Musculoskeletal Pain Index  58 Ovariohysterectomy (Pain Management Protocol Example)  518–­519 Femoral‐­Saphenous Nerve Complex Block  160, 161 Fentanyl  100 Patches  100, 264 Ferret Grimace Scale  86 Pain Scoring  355 Painful Behavior  353 Firocoxib  107 First‐­Pass Effect  96 Fish Amphibian Analgesia  371 Common Analgesics in  373 Normal Appearance  84 Pain Behavior and Clinical Signs  373 Pain Score  84 Flavonoids  479

Food and Fiber Species Analgesia for  315 Pain Recognition and Scoring  63, 80 Forelimb Amputation  196, 197 Description  452 Pain Management Protocol Example  523–­524 Fractures  246 French Association for Animal Anesthesia and Analgesia Pain Scoring System  56 Frontal Nerve (Supraorbital Foramen) Block  140, 141 Frunevetmab (Solensia)  117 Full Opioid Agonists  97, 98

g

Gabapentin  111, 200, 269, 283, 342, 367, 397 Gabapentinoids  111, 269, 483 Gait Analysis  53, 425 Gastrointestinal (Colic and Ulcers) Pain (Equine)  297 Procedures  190, 191 Gate Control Theory  2, 28 G‐­Coupled Protein Receptors (GPR)  481 General Wound Healing  415 Gerbils Painful Behavior  355 Pain Scoring  356 Glasgow Composite Measure Pain Scale Short and Long Forms (Canine)  56, 65 Short and Long Forms (Feline)  57 Glucosamine/Chondroitin  491 Glycine Receptors (GlyR)  481 Goniometry and Muscle Girth  419

Index

Goniometric Measurements (Canine)  445 Limb Circumference  447 Grapiprant  108 Great Apes  398 Green Lipped Mussel Extract  492 Grimace Scale Feline  57, 66–­69 Ferret  86 Horse  75, 76, 79 Mouse  87 Rabbit  88 Guinea Pigs Painful Behavior  356 Pain Scoring  356 Gut‐­Brain Axis  38

h

Half‐­life  96 Hamsters Painful Behavior  356 Pain Scoring  356 Harm Reduction Education (HRE)  485 Havel Spinal Needle  132 Headaches and Migraines in Animals  259 Health‐­Related Quality of Life (VetMetrica)  62 Heart Rate  52 Helsinki Chronic Pain Index  57 Hemilaminectomy (Pain Management Protocol Example)  522–­523 Hindlimb Amputation  197, 198 Description  451 Hip Dysplasia  298 History (Patient)  49 Horse Analgesia for Castration  167 Caudal Epidural  167, 168 Common Painful Conditions and Procedures  295

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Grimace Scale  75, 76, 79 Locoregional Anesthetics and Techniques  294 Pain Behavior  74 Pain Score  81 Somatic Pain Indicators  75 Visceral Pain Indicators  75 Hospice and Palliative Care  507 Analgesia for the Dying Patient  512 Caregiver Education and Training  510 Delivery of Care  509 Euthanasia and Analgesia for the Dying Patient  512 Natural Death  514 Pain Management for the Dying Animal  514 Pain Recognition and Management  511 Patient Presentation and Evaluation  509 Planning of Care  509 Setting Up the Physical Environment  510 Social Environment  510 Support for the Family  510, 515 Technicians’ Roles  509 Veterinary Staff  508 Work Areas  508 Hospitalized (Critically Ill and)  457 HQHVSN (High‐­Quality/ High‐­Volume Spay‐­Neuter)  277 Program Operation  283 Human‐­Animal Bond  50 Hyaluronic Acid  440 Hydrocodone  101 Hydromorphone  100 Hydrotherapy (Aquatic Therapy)  444 Benefits  444 Hyperalgesia  24, 33

i

Ibuprofen  229 ICU Psychosis  234 Incisional Line Block  143, 144, 222 Induction (Surgical Pain)  183 Inferior (Caudal) Alveolar Nerve Block  133, 200 Extra‐­oral Technique  133, 134, 135 Intra‐­oral Technique  134 Inflammatory Pain  255 Infraorbital Nerve Block  136, 137 Infusion of the Teat Cistern (Cattle)  321 In‐­Home Pain Assessment for Cats (AAHA)  64 Injectable Hydrogel Microparticles  441 Integrative Medicine  465 Intercostal Blocks  144, 145 Interleukin‐­1 Receptor Antagonist Protein (IRAP)  440 International Academy of Pain Management (IVAPM)  6 Interpleural Block  146 Intraperitoneal Lavage  143, 222 Intratesticular and Spermatic Cord Block  147 Intratesticular Block (Sheep and Goats)  330 Intravenous Regional Anesthesia (IVRA) (Cattle)  320 Invertebrate Analgesia  372 Analgesics in Invertebrates  374 Analgesia Strategies  375 Inverted L‐­Block or 7‐­Block (Sheep and Goats)  328

533

534

Index

j

Joint Mobilizations and Chiropractic  437 Examples  450 Range of Motion‐­Passive  438 Forelimb Description  452 Hindlimb Description  451

k

Ketamine Acute Pain  200 Anesthesia  6 Donkeys  308 Exotic Companion Animals  357, 364, 370, 392 Food and Fiber Species  319, 327, 334, 340 HQHVSN  281 NMDA Antagonist  114 Zoo Animals  392 Key Nutritional Factors  468 Kinesio Taping  439 Kirby’s Rule of  20 239 Kratum  491

l

Laboratory Animals Pain Score  85, 87, 88 Laminitis Pain (Equine)  75, 78, 299 Land Treadmills  443 Lateral Thoracotomy (Pain Management Protocol Example)  521–­522 Lidocaine  110, 111, 128, 200, 290, 294, 295 CRI  243 Patches  264 Limb Blocks  160 Circumference  447 Lipid Solubility (Opioids)  221

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Liverpool Osteoarthritis in Dogs  57 Loading Dosage  96 Local Anesthesia Techniques  185 Anesthetic Agents  319, 339 Anesthetics  110, 127, 128, 282 Adjunctive Agents  129 Advantages  127, 128 Maximum Recommended Dose  130 Mixing  129 Mode of Action  131 and Regional Analgesia (ER/ICU)  244 and Regional Anesthesia (Sheep and Goats)  327 and Regional Anesthetics (Zoo Animals)  401 and Regional Blocks  127, 222, 229 Equipment Selection  131 Regional Blocks (Rodents and Ferrets)  352, 358 Locomotion Scoring of Dairy Cows  72 Locoregional Anesthetics and Techniques (Equine)  294 Low–­Stress Certifications Cat‐­Friendly Certificate Program  13 Fear Free Certification  13 Low‐­Stress Handling Certification  13 Lumbosacral Epidural Block (Swine)  334

m

Machine Learning and Artificial Intelligence  54 Macronutrients  470

Magnesium  491, 492 Major Cannabinoids  478 Major Palatine Block (Small Animal)  137, 138 Maladaptive Pain  33 Malignant Pain (Oncologic/)  256 Mandibulectomy/ Maxillectomy  200 Mandragora  1, 3 Manual Therapy  436 Maropitant  115, 245, 367, 393 Massage (Therapeutic)  438 Indications  439 Precautions and contraindications  439 Technique  452 Mavacoxib  107 Maximum Dosage for Local Anesthetics  223 Recommended Dose (Local Anesthetics)  130 Mechanism of Action (MOA) Local Anesthetics  131 Medications  96 Medetomidine  112 Medical Interventions (Therapeutic)  439 Medications Administration in Zoo Animals  385–­388 Avian Analgesia  359, 363, 365 Camelids  337–­342 Cattle  317–­325 Common Analgesics Amphibians  371 Birds  363, 365 Exotic Companion Animals  351, 356, 357, 368, 370 Fish  373 Invertebrates  374 Rabbits  351

Index

Rodents  356, 357 Zoo Animals  385–­388, 390–­393 Donkeys  304, 306–­308 Equine  289, 290, 292, 305 HQHVSN  277, 279, 280, 281, 282, 283 Sheep and Goats  326, 327 Swine  332, 334, 335, 336, 337 Transdermal  264 Melatonin  493 Melbourne Pain Scale (University of)  56 Meloxicam  107, 229, 306, 327, 332, 338, 352, 358, 365, 369, 392 Memantine  115 Meningitis  259, 260 Meperidine (Pethidine)  99, 291, 306, 326, 332, 337, 365, 369 Mepivacaine  110, 128 Mesotherapy  263 Metabolism (Opioids)  220 Metamizole (Dipyrone)  117 Methadone  99, 292, 306, 326, 332, 337, 365, 369 Methylprednisolone  295 Mice Painful Behavior  354 Pain Scoring  355 Microbial‐­Derived Metabolites  38, 39 Microbiota Health  471 Microbiome  35–­38, 41, 42 Micronutrients  470 Middle Mental Foramen Nerve Block  135, 136 Minimally Invasive Procedures  195

n

Nalbuphine  105, 290, 306, 326, 332, 337, 365, 369, 392 Nalmefene  105

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Naloxone  105, 280, 307, 392 Naltrexone  105 Narcotic  97 National Association of Veterinary Technicians in America (NAVTA)  4 Natural Death  514 N‐­Butylscopolammonium Bromide (NBB)  293 Neonatal Pain Pathways  227 Patients  227 Resuscitation  225 Neoplasia  511 Nerve Blocks (Cattle)  318 Stimulating Needle  132 Neurokinin‐­1 Inhibitors  115, 270 Neurological Conditions  456 Neuropathic Pain  33, 255 Neuroplasticity  31 Neurotransmitters  39 NMDA Receptor Antagonists  290, 293 N‐­Methyl‐­D ‐­Aspartate (NMDA) Antagonists  114, 269, 319, 334, 340 Receptors  228, 481, 482 Nociceptive Pathway  18, 23, 27 in Cattle  319 Pathway (Modulation)  18–­21, 23, 27, 28, 38 Pathway (Perception)  19–­21, 24, 27–­30, 40 Pathway (Transduction)  18–­20 Pathway (Transmission)  19–­21, 23, 27, 28 Withdrawal Reflex  53 Nociceptors  17–­20, 24, 25–­26, 33

Nocita  110, 128 Non‐­domestic Animals (Pain Recognition in)  382, 383 Non‐­human Primates (NHP) (Old World and New World)  399 Nonruminant Ungulates  403 Non‐­species‐­specific Pain Assessments  52 Non‐­steroidal Anti‐­ inflammatory Drugs (NSAIDs)  106, 108, 219, 224, 229, 245, 265, 279, 281, 292, 305, 317, 327, 332, 338, 352, 358, 365, 369, 392, 397, 400 Normal Appearance Amphibians and Fish  84 Birds  78 Horses  74 Reptiles  82 Nursing Care ER/ICU Setting  239 Exotic Companion Animals  350 Nutraceuticals  271, 465, 489, 491 Nutrient‐­Focused Diets  471 Nutrition Assessment  466 Complete and Balanced  467

o

Obesity  468 Old World and New World Non‐­human Primates (NHP)  399 Omega‐­3 Fatty Acids  489 Oncologic/Malignant Pain  256 Oncology (Palliative, Hospice Care and)  458, 459

535

536

Index

Opioids  97, 200, 219–­221, 228, 244, 266, 279, 280, 289, 290, 306, 307, 317, 326, 332, 337, 352, 358, 365, 369, 392 Administration (Routes of)  220 Agonists (Full)  97, 98 Alfentanil  100 Antagonists  105, 245 Buprenorphine  102, 291 Buprenorphine Patches  105 Buprenorphine (Sustained or Extended Release)  104 Butorphanol  105, 290, 398 Carfentanil  100 Codeine  101 Fentanyl  100, 292 Fentanyl Patches  100, 264 Hydrocodone  101 Hydromorphone  100 Meperidine (Pethidine)  99, 291 Methadone  99, 292 Mixing  106 Morphine  99, 291, 292 Nalbuphine  105 Nalmefene  105 Naloxone  105 Naltrexone  105 Oxycodone  101 Oxymorphone  100 Partial Agonist  102 Receptors  482 Remifentanil  100 Sufentanil  100 Tapentadol  102 Tramadol  101, 291, 308, 342, 366, 398 Use In Animals (Oral)  101 Oral Opioid Use In Animals  101 Pain Scale (Canine/ Feline)  59 Orthopedic Conditions  455, 456

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Disability Index (Cincinnati)  62 Procedures  196 Orthosteric Binding Site  96 Osteoarthritis (OA)  255, 298, 511 Chronic OA Pain Canine  517 Feline  517 in Dogs (Liverpool)  57 Ovariohysterectomy (Feline)  517 Ovine (Sheep) and Caprine (Goat) Common Painful Surgeries  326, 328 Continuous Rate Infusions  330, 331 Medications  326 Multimodal Analgesia  331, 332 Regional and Local Anesthesia  327 Withdrawal Period  333 Oxycodone  101 Oxymorphone  100

p

Pain Acute  32, 33, 179, 181, 185, 200, 243, 480 Adaptive  32, 33 Affect and Intensity  48 Assessment  418, 511 Canine  56, 70 Cats (AAHA & In‐­Home)  64 Chronic  260 Clinical Scoring Tools (Canine and Feline)  55 Dairy Cows (Locomotion Scoring)  72 Donkeys  304, 305 Equine  289 ER Setting  234 Exotic Species  77, 85, 86

Feline  57, 66–­69 Ferrets  353, 355 Fish  84, 373 Food and Fiber Species  63, 80 Gerbils  355 Guinea Pigs  356 Hamsters  356 Horses  74, 75, 76, 79, 81 Intensity and Affect  48 Lab Animals  85, 87, 88 Location  48 Mice  354, 355 Non‐­domestic Animals  382, 383 Non‐­species‐­specific  52 Oral (Canine/Feline)  59 Rabbits  349, 350 Rats  355 Reptiles  82, 83 Sheep 73,  80 Small Exotic Mammals  85 Swine  73 and Zoo Animals  384 Behavior Amphibians and Fish  84 Birds  77, 78 Camelids  71 Companion Animals  59 Donkeys  305 Equine  74 Exotic Species  85, 86 Horses  74 Lab Animals  85, 87, 88 Reptiles  82 Rodents  353 Sheep and Goats  71 Small Exotic Mammals  85 Swine  73 Biomarkers  53 Catastrophizing  29, 30 Central Sensitization  24, 31, 33, 36 Chronic  33, 34, 253 Assessment  260

Index

Conditions  255 Management (Cannabinoid Role)  481 Pharmacological Interventions  262 Scoring  56, 58 Vacation  262 Complex Regional Pain Syndrome  35 Cutaneous  202, 211 Domains  48 Dysfunctional  255 Inflammatory  255 Intensity and Affect  48 Location  48 Maladaptive  33 Management Dying Animal  514 Hospice and Palliative Care  511 Protocol Examples  517 Neuropathic  33, 255 Perception  19–­21, 24, 27–­30, 40 Persistent Postsurgical  34 and Personality (Disposition and)  48 Physiology and Psychology  17 Radicular  34 Recognition and Scoring  47 Referred  32 Scoring and Assessment  420 Somatic  32 and Stress (Relationship Between)  29 Surgical  181–­185, 296 Temporal Dimensions  48 Types  32 Visceral  32, 75 Windup (ER)  242 Palliative Care (Hospice)  507

q

Quantitative Sensory Testing  52

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r

Rabbits Common Analgesics  351 Continuous Rate Infusions  353 Painful Behavior  349, 350 Pain Scoring  350 Regional and Local Anesthesia  352 Radial, Ulnar, Median, and Musculocutaneous (RUMM) Nerve Block  166 Radicular Pain  34 Radiosynoviorthesis  441 Range of Motion‐­Passive (Joint)  438 Forelimb Description  452 Hindlimb Description  451 Rats Painful Behavior  355 Pain Scoring  355 Receptor Cannabinoid  475 Glycine (GlyR)  481 N‐­Methyl‐­D ‐­Aspartate (NMDA)  228, 481, 482 Opioid  482 Peroxisome Proliferator‐­ activated (PPAR)  482 Serotonin (5‐­HT)  482 Transient Receptor Potential (TRP) Cation Channel  482 Recognizing Behavior in Bird Species  360 Pain in Non‐­domestic Animals  382, 383 Recovery (Surgical Pain)  183 Recreational Cannabis  484 Referred Pain  32 Regenerative Medicine and Biological Treatments  439

Regional and Local Analgesia (ER/ICU)  244 and Local Anesthesia and Analgesia Techniques (Cattle)  319 and Local Anesthesia (Sheep and Goats)  327 and Local Anesthesia (Zoo Animals)  401 and Local Blocks  127, 222, 229 Equipment Selection  131 and Local Blocks (Rodents and Ferrets)  352, 358 Rehabilitation Canine Veterinary Technician Certifications  12 Equine Veterinary Technician Certifications  12 Exercises for Early Rehabilitation  453, 454 Physical  10, 15, 245, 271, 411 Aging Patient  427 Applications in Veterinary Medicine  413, 414 Assistive Devices  427, 429 Client Communication and Activity Modification  417 Common Conditions and Therapeutic Modalities  413, 414 Environmental Management  430 Environmental Modifications  430 Gait Analysis and Movement  425 Goniometry and Muscle Girth  419 Hydrotherapy (Aquatic Therapy)  444 Kinesio Taping  439

537

538

Index

Rehabilitation (cont’d) Lameness  425, 426 Land Treadmills  443 Manual Therapy  436 Musculoskeletal System  422 Pain and Disability Scoring and Assessment  420 Patient Assessment  418 Patient Management  427 Photobiomodulation  433, 434 Physical Rehabilitation Scope of Training  411 Sample Rehabilitation Guidelines  454 Structural and Postural Evaluation  424 Superficial Thermal Therapies  431 Team Approach to Care  413 Therapeutic Exercise and Aquatic Therapy  442 Therapeutic Massage  438 Therapeutic Medical Interventions  439 Tissue Injury  414 Veterinary Diagnosis  418 Veterinary Technician Role  413 Sample Guidelines  454 Veterinary Technician Specialist (VTS) Academies Academy of Physical Rehabilitation Veterinary Technicians (APRVT)  11 Relationship Between Pain and Stress  29 Remifentanil  100 Reproductive Tract Surgery  186, 187 Reptile Analgesia  367 Causes of Pain  368 Common  370

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s

Sacrococcygeal Block  147, 148 Sample Rehabilitation Guidelines  454 Sciatic Nerve Block  162, 163, 164 Scoring Pain and Discomfort (Zoo Animals)  384 Selective Serotonin Reuptake Inhibitors (SSRIs)  118, 268 Sensory Perception in the Skin  202 Serotonin–­Norepinephrine Reuptake Inhibitors (SNRIs)  118, 268 Serotonin (5‐­HT) Receptor  482 Setting Up the Physical Environment (Hospice and Palliative Care)  510 Sheep (Ovine) and Goats (Caprine) Common Painful Surgeries  326, 328 Continuous Rate Infusions  330, 331 Medications  326 Alpha‐­2 Adrenergic Agonists  327 NMDA Antagonists  327 NSAIDs  327 Opioids  326 Multimodal Analgesia  331, 332 Regional and Local Anesthesia  327 Bier Block  329 Caudal Epidural  329 Cornual Block  327 Intratesticular Block  330 Inverted L‐­Block or 7‐­Block  328 Paravertebral Nerve Block  328 Visceral Pain  326 Withdrawal Period  333

Sheep Grimace Scale  73, 80 Simbadol  104 Skin Infections  204–­206 Sleep Deprivation  241 Small Exotic Mammals Pain Score  85 Small Ruminants and Camelids (Pain Behavior)  71 Cornual Nerve Block  171 Social Environment (Hospice and Palliative Care)  510 Resilience and Pain  35 Soft Tissue Injuries  247 Solensia (Frunevetmab)  117 Somatic Pain  32 Pain Indicators (Equine)  75 Specificity Theory  2 Spermatic Cord Block (Cattle)  322, 324 Spinal Anesthesia  152 Cord (Anatomy)  21 Disease  197, 198 Surgery  197, 198, 199 Spinoreticular Tract  24 Spinothalamic Tract  22, 23 Splenectomy (Pain Management Protocol Example)  521 Splinting (Bracing and)  429 Stress and Anxiety on Pain  29 and Pain (Relationship Between)  29 Physiological Response  240 Structural and Postural Evaluation (Physical Rehabilitation)  424 Sufentanil  100 Superficial Thermal Therapies  431–­433 Support for the Family (Hospice and Palliative Care)  510, 515

Index

Surgical Pain  181–­185, 296 Induction  183 Maintenance  183 Postoperative Analgesia  183 Premedication  182 Recovery  183 Pain (Equine)  296 Research Anesthetist (SRA)  11 Sustained or Extended Release Buprenorphine  104 Swelling and Edema  248 Swine Analgesia  405 Common Painful Procedures  332 Continuous Rate Infusions  335 Lumbosacral Epidural Block  334 Medications  332, 334–­337

t

Tail Surgery  198, 200 Take‐­home Analgesics  184 Tapentadol  102, 266 TCVM Veterinary Technician Programs  12–­13 Team Approach to Care (Physical Rehabilitation)  413 Teat Block (Cattle)  321 Temporal Dimensions (Pain)  48 Summation  53 Tendons and Ligaments  416 Terpenoids  479 Tetracaine  110 Therapeutic Exercise and Aquatic Therapy  442 Principles and Application  442 Index  96

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Massage  438 Indications  439 Precautions and Contraindications  439 Technique  452 Medical Interventions  439 Ultrasound  435 Thermal Therapies (Superficial)  431–­433 Thoracic Paravertebral Block  157 Procedures  191–­193 Regional and Local Blocks  144 Tibial Plateau Leveling Osteotomy (Pain Management Protocol Example)  520 Tiletamine  114 Tissue Distribution  96 Injury  414 Tolazoline  113 Tramadol  101, 266, 291, 308, 342, 366, 398 Transdermal Medications  264 Transduction (Nociceptive Pathway)  18, 19, 20 Transient Receptor Potential (TRP) Cation Channel  482 Transmission (Nociceptive Pathway)  19, 20, 21, 23, 27, 28 Transversus Abdominis Plane (TAP) Block  158, 159, 224 Trauma Patients  247 Trazodone  119, 283 Treatment of Cutaneous Pain and Pruritus  211 Options (Myofascial Trigger Points)  450 of Pain in Zoo Animals  385

Strategies (Fish and Amphibian Analgesia)  372 Tricyclic Antidepressants (TCAs)  118, 268 Trunk Activity (Elephants)  397 Turmeric (Curcumin)  490

u

Ulcers (Gastrointestinal Pain in Equine)  297 Ulnar Nerve Block (RUMM)  166 Ultrasound (Therapeutic)  435 Ungulates (Exotic)  402 Nonruminant  403 Ruminant  404 University of Melbourne Pain Scale  56 University of Tennessee Companion Animal Pain Management Certificate Program  11 Urinary Disease  194, 195 Tract Obstruction (Feline)  247

v

Ventral Horn  20, 22, 23 Veterinary Anaesthesia and Analgesia (MSc, PgDip, PgCert, PgProfDev)  13–­14 Diagnosis  418 Pain Practitioner (Certified) 6,  9 Staff (Hospice and Palliative Care)  508 Social Workers  508, 515 Technician Role (Physical Rehabilitation)  413 Specialist (VTS)  4

539

540

Index

Veterinary (cont’d) Specialist (VTS) Academies  10 Academy of Laboratory Animal Veterinary Technicians and Nurses (ALAVTN)  10 Academy of Physical Rehabilitation Veterinary Technicians (APRVT)  11 Academy of Veterinary Technicians in Anesthesia and Analgesia (AVTAA)  10 VetMetrica Health‐­Related Quality of Life  62 Visceral Pain  32, 75 Pain Indicators (Equine)  75 Pain (Sheep and Goats)  326 Vocalizations and Trunk Activity (Elephants)  397

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Volume Expansion and Buffering (Local Anesthetics)  129

x

w

y

Washout Period (NSAIDs)  108 Weight Loss  271, 468 White Matter  20, 23 Wildlife  406 Windup Pain (ER)  242 Withdrawal Period Cattle  324, 325 Sheep and Goats  333 Swine  337 Withdrawal Reflex (Nociceptive)  53 Work Areas (Hospice and Palliative Care)  508 World Small Animal Veterinary Association (WSAVA) Certificate in Pain Management  12 Wounds (Chronic)  259 WSAVA Global Pain Council (GPC)  5

Xylazine  112, 282, 307, 318, 327, 334, 339, 392

Yohimbine  113

z

Zenalpha  113 Zolazepam  114 Zoo Animals Adjunctive Therapies  388 Choosing a Pain Regimen  389 Common Analgesics  390–­393 Exotic Animal Formulary  390–­393 Local and Regional Anesthetics  401 Medication Administration  385–­388 Pain Recognition and Scoring  384 Treatment of Pain  385 Zorbium  104, 264

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