Pain Management in Veterinary Medicine PDF 2024

PA I N M A N A G E M E N T IN VETERINARY MEDICINE Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia 7th October 2024 LEARNING OBJECTIVES  Define the terms pain, analgesia, hyperalgesia & allodynia  Understand the various com...

PA I N M A N A G E M E N T IN VETERINARY MEDICINE Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia 7th October 2024 LEARNING OBJECTIVES  Define the terms pain, analgesia, hyperalgesia & allodynia  Understand the various components of the pain experience  Describe the different types of pain: acute versus chronic, nociceptive, inflammatory and neuropathic  Describe the physiology underling nociception, transmission of nociceptive signals, central and peripheral sensitisation and the descending inhibition of nociception  Outline behaviours associated with pain in domestic species  Understand how to use pain scoring systems to recognise patients with acute & chronic pain  Understand how to assess the severity of pain based on the (patho)physiology of the condition LEARNING OBJECTIVES  Define the terms pre-emptive analgesia and multimodal analgesia  Describe the mechanism of action, uses and potential adverse effects of the non-steroidal anti-inflammatory drugs, paracetamol, opioids, ketamine, local anaesthetics, gabapentin, pregabalin, amantadine, bedinvetmab, frunevetmab  Describe the use of alternative pain management therapies such as acupuncture & physiotherapy techniques such as (hot & cold therapy, laser therapy, massage, TENS)  Understand the approach to analgesic planning and create analgesic plans for commonly encountered clinical scenarios in domestic species INTRODUCTION Recent improvement in pain management… Pain still under recognized & under treated Lack of licensed drugs Lack of knowledge £££ Image from: Rights of Man - Dr. Paul Clayton (drpaulclayton.eu) DEFINITIONS “ PAIN is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” (International Association for the Study of Pain, 2018) ≠ “ NOCICEPTION is the neural process of encoding and processing noxious stimuli “ (Loeser & Treede, 2008) Image from: Taylor S, Gruen M, KuKanich K, et al. 2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery. 2024;26(4). PAIN PHYSIOLOGY PA I N P H Y S I O L O G Y Image from: Postoperative and acute pain management: part 1 | Vet Times PA I N P H Y S I O L O G Y TRANSDUCTION: conversion of noxious stimuli to an action potential at the level of the nociceptors Nociceptors (specialised free nerve endings of 1st order neurons) Skin, muscles, joints, viscera, meninges Image from: https://humanbiomedia.org Image from: https://www.slideshare.net/adityapoltek/pain- transduction-transmission PA I N P H Y S I O L O G Y TRANSMISSION Poorly localised , dull pain Well localised sharp pain Image from: Y.A. Kulkarni, S.V. Suryavanshi, S.T. Auti, A.B. Gaikwad, Chapter 9 - Capsicum: A Natural Pain Modulator, Editor(s): Ronald Ross Watson, Sherma Zibadi, Nutritional Modulators of Pain in the Aging Population, Academic Press, 2017,Pages 107-119, ISBN 9780128051863, https://doi.org/10.1016/B978-0-12-805186-3.00009-6. PA I N P H Y S I O L O G Y DORSAL HORN SPINAL CORD Synapsis with 2nd order neurons→ ascending tract to brain Intersegmental neurons & contralateral projecting neurons Interneurons (excitatory or inhibitory) Descending control pathways motoneurons: reflex arc Image from: Pain as a Perceptual Experience | Anesthesia Key (aneskey.com)  Thalamocortical PA I N P H Y S I O L O G Y structures MODULATION ↑or ↓ of pain sensation inhibition or facilitation of nociceptive signals Occurs at ≠ level Descending Inhibitory Pathways Image from: Benarroch, Eduardo E.. “Descending monoaminergic pain modulation.” Neurology 71 (2008): 217 - 221. PA I N P H Y S I O L O G Y MODULATION The GATE CONTROL THEORY (Melzack & Wall, 1965) Acupuncture, TENS, Massage Image from: Vervaat, Fabienne & Gaag, Antal & Teeuwen, Koen & Suijlekom, Hans & Wijnbergen, Inge. (2022). Neuromodulation in patients with Refractory Angina Pectoris – A Review. European Heart Journal Open. 3. 10.1093/ehjopen/oeac083. PA I N P H Y S I O L O G Y PROJECTION LIMBIC SYSTEM Nociceptive info transported to the brain RETICULAR FORMATION HYPOTHALAMUS PONS Image from: https://humanbiomedia.org/  PA I N P H Y S I O L O G Y PERCEPTION Brain's process of integrating the nociceptive info or the conscious processing of pain Cortex Image from: Achim Schmidtko, Irmgard Tegeder, Gerd Geisslinger, No NO, no pain? The role of nitric oxide Image from: Pain as a Perceptual Experience | and cGMP in spinal pain processing, Trends in Neurosciences, Volume 32, Issue 6, 2009,Pages 339-346 Anesthesia Key (aneskey.com) PAIN CLASSIFICATION PA I N C L A S S I F I C AT I O N ACUTE vs CHRONIC PAIN ACUTE PAIN Results of trauma, surgical or infectious events Starts abruptly, resolves in days/weeks Self-limiting, biological purpose CHRONIC PAIN Persists beyond normal time of healing/absence of healing > 1-3 months in duration Disease PA I N C L A S S I F I C AT I O N NOCICEPTIVE PAIN INFLAMMATORY PAIN Protective function from potential damage Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 PA I N C L A S S I F I C AT I O N SOMATIC PAIN Well localised, aching, sharp, intense Superficial or Deep Image from: https://aneskey.com/gastrointestinal-system-and-acute- visceral-pain/ VISCERAL PAIN Dull, diffused, poorly defined sensation Referred pain PA I N C L A S S I F I C AT I O N NEUROPATHIC PAIN Caused by injury of the somatosensory system (i.e., peripheral nerves, spinal cord or brain) Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 PA I N C L A S S I F I C AT I O N ALLODYNIA = Pain sensation in response to a non painful stimulus HYPERALGESIA = Exagerated pain sensation in response to a normally painful stimulus Image from: Lolignier, Stéphane & Eijkelkamp, Niels & Wood, John. (2014). Mechanical allodynia. Pflugers Archiv : European journal of physiology. 467. 10.1007/s00424-014-1532-0. PA I N C L A S S I F I C AT I O N NEUROPATHIC PAIN Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 PA I N C L A S S I F I C AT I O N Image from: Costigan, Scholz, Woolf (2009) Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage. Annual Review of Neuroscience, Volume 32. PA IN A S S ESS M E NT PA I N A S S E S S M E N T ? MANY CHALLENGES… Absence of verbal communication Aggressive/Stoic patients Species variations (prey vs predator) Individual normal behaviour vs hospitalisation Fear/anxiety Emergency delirium/Dysphoria/Euphoria Subjectivity of the assessment’s methods PA I N A S S E S S M E N T PHYSIOLOGICAL PARAMETERS Not specific… Heart rate Arterial blood pressure Respiratory rate Plasma cortisol, catecholamine levels, glucose, insulin, endorphins Use in ASSOCIATION with BEHAVIOURAL PARAMETERS PA I N A S S E S S M E N T BEHAVIOURAL ASSESSMENT Observation Interaction Response to manipulation Pain behaviour are species- specific Images courtesy of Dr. Teela Jones A C U T E PA I N A S S E S S M E N T I N D O G S & C AT S Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 U N I D I M E N S I O N A L v s M U LT I D I M E N S I O N A L PA I N SCALES Images from: Pain Scale: What It Is and How to Use It (healthline.com) PA I N A S S E S S M E N T MULTIDIMENSIONAL PAIN SCALES: ACUTE PAIN  Assess intensity, emotional & sensory components of pain Includes interactive components and behavioural categories Determine the cut off point beyond which the animals require analgesia/further analgesia Subjective? Training PA I N A S S E S S M E N T Glasgow Composite Pain Scale (also short form) UNESP- Botucatu Multidimensional Composite Pain scale Colorado State University Acute Pain scale (not validated) PA I N A S S E S S M E N T PA I N A S S E S S M E N T FACIAL PAIN SCALES (GRIMACE SCALES) Observation of the subject from a distance Different action units  No direct interaction Developed in many species Image from: Turner, Patricia V. et al. “A Review of Pain Assessment Methods in Laboratory Rodents.” Comparative medicine (2019) PA I N A S S E S S M E N T 34 PA I N A S S E S S M E N T CHRONIC PAIN CHRONIC PAIN SCALES Helsinki Chronic Pain Index (HCPI) Challenging to assess Canine Brief Pain Inventory (CBPI) Subtle changes Cincinnati Orthopedic Disability Index (CODI) Effect on behaviour & quality of life Health-Related Quality of Life (HRQL) Owner involvement/questionnaires Liverpool Osteoarthritis in Dogs (LOAD) Feline Musculoskeletal Pain Index (FMPI) C H R O N I C PA I N A S S E S S M E N T I N D O G S & C AT S Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 PA I N A S S E S S M E N T PRESSURE MATS/ FORCE PLATE for GAIT ANALYSIS ACCELLEROMETRY QUANTITATIVE SENSORY TESTINGS - Response to application of mechanical, thermal stimuli (i.e. algometers) - Semi-objective methods PA I N A S S E S S M E N T WHEN? - At admission, before, after the procedure HOW OFTEN? - During recovery phase: q 15’ then q 60’ for the first hours, then q 4h? - Before next analgesic medications is due - In between dosages - If additional analgesia has been administered: reassess after 15-30’ CONSISTENCY: ideally same person(trained), same methods PA IN T REATM E NT W H Y S H O U L D W E T R E AT PA I N ? To avoid: SNS & Stress response activation Immunodepression Delayed wound healing Inflammation Image from: Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, Decrease appetite/anorexia assessment and treatment of pain. J Small Anim Pract, 64: 177- 254. https://doi.org/10.1111/jsap.13566 Deterioration of quality of life & human-pet relationship ↑ Hospitaliza on mes ↑ £££ PA I N T R E AT M E N T PRE-EMPTIVE ANALGESIA Administration of analgesics drugs BEFORE the onset of the noxious stimulus Reason to administer analgesic drugs in premedication Image from: Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician. 2001 May 15;63(10):1979-84. PMID: 11388713 PA I N T R E AT M E N T MULTIMODAL ANALGESIA Use > than one pharmacological class of analgesic medications targeting different receptors along the pain pathway Produce superior analgesia To reduce individual class-related side effects Image from: cliniciansbrief.com PA I N T R E AT M E N T O P T I O N S Opioids Local anaesthetics Lidocaine (systemic administration) NSAIDs Paracetamol Ketamine α2 adrenoceptor agonists Gabapentin/ pregabalin Image from: https://picryl.com/media/questions- Amantadine demand-doubts-emotions-2ea8c6 Tramadol OPIOIDS Reduction CORTEX pain perception THALAMUS DORSAL HORN RVM & PAG Activation of Reduce excitatory descending neurotransmitter release inhibitory Hyperpolarization post pathways synaptic membrane Inhibition of PERIPHERAL NOCICEPTORS ascending nociceptive input Acute pain Image from: Schäfer M. Mechanisms of action of opioids. In: Evers AS, Maze M, Side effects Kharasch ED, eds. Anesthetic Pharmacology: Basic Principles and Clinical Practice. Cambridge University Press; 2011:493-508. OPIOID FREE ANAESTHESIA Human medicine : Short term use of opioids Acute pain Side effects Hyperalgesia Addiction risk TRAMADOL Weak mu-receptor agonist Weak alpha 2 agonist action Inhibitor of norepinephrine & serotonin reuptake in the CNS NMDA receptor antagonism? Active metabolite minimal in dogs & cats after oral administration Analgesia? Serotonin Syndrome risk Vomiting, Drowsiness ALPHA 2 ADRENORECEPTOR AGONISTS Analgesia shorter lasting compared to sedation? Spinal (pre & post synaptic) & Supraspinal Adjunctives : synergistic with opioids Acute Pain Side effects: Sedation, Bradycardia & Blood pressure changes, emesis K E TA M I N E Non- competitive NMDA receptor antagonist Interaction with many other receptors (opioid, nicotinic & muscarinic…)  Acute & Chronic pain Image from: Earnshaw, Berton & Supervisor, & Bressloff, Paul. Diffusion model of AMPA receptor trafficking in the postsynaptic membrane. LOCAL ANAESTHETICS Mechanism of action: Na+ channel blocker: block TRANSMISSION of the nociceptive inputs LOCAL ANAESTHETICS Gold standard to prevent transmission of pain Decrease other analgesic drugs peri-operative requirements £ Training required Narrow therapeutic index: work below toxic doses to avoid side effects on CNS and cardiovascular system Lidocaine (fast onset, shorter duration) vs Bupivacaine & Ropivacaine (slower onset, longer duration) ≠ administration techniques: Topical, Local blocks, Loco-Regional anesthesia LOCAL ANAESTHETICS Different properties based on: Dissociation constant (pKa) (onset) Lipid solubility (potency) Protein binding (duration) Image from: Veterinary Anaesthesia - Principles to Practice, 2nd Edition - Softcover Dugdale, Alexandra H. A.; Beaumont, Georgina; Bradbrook, Carl; Gurney, Matthew LIDOCAINE BUPIVACAINE ROPIVACAINE ONSET 2-5 min 20 min 20 min DURATION 1h 4-8 h ? 4 -8 h ? DOG 4-6 mg/kg DOG 2 mg/kg DOG 3 mg/kg MAX DOSE CAT 2-3 mg/kg CAT 1.5 mg/kg CAT 1.5 mg/kg LOCAL ANAESTHETICS ADVERSE EFFECTS Systemic toxicity (overdose, IV administration, species) Nerve & local tissue injury Local haemorrhage Infections Allergic reactions (preservatives, esters local anaesthetics) LIDOCAINE TOXICITY Calculate your volume before, staying below toxic dose! BUPIVACAINE: cardiac & CNS signs @ = time Aspirate before injection, confirm absence of blood Image from: Thurmon John C. et others (2015) Veterinary Anesthesia and Analgesia : The Fifth Edition of Lumb and Jones. Fifth ed. Ames Iowa: Wiley Blackwell : John Wiley & Sons. LIDOCAINE Bolus + Constant Rate Infusion (CRI) Blockage of Na+ channels Anthiarrhythmic (class 1B) Anti-inflammatory Promotion of gut motility Nausea & Vomiting CAREFUL use in CATS: toxicity!! N S A I D s ( N O N - S T E R O I D A L A N T I - I N F L A M M ATO R Y D R U G S ) Wide availability, long duration of action, easy to administer, no sedation, not controlled, £ Acute & Chronic pain Image from: Scales C. (2021) Know your NSAIDs, The Veterinary Nurse, Volume 12 Issue 4 N S A I D s ( N O N - S T E R O I D A L A N T I - I N F L A M M ATO R Y D R U G S ) Adverse effects: Vomiting, diarrhoea, anorexia, gastro-intestinal ulceration & perforation Renal injury Drug induced liver injury Coagulation Image from: Taylor S, Gruen M, KuKanich K, et al. 2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery. 2024;26(4). doi:10.1177/1098612X241241951 N S A I D s ( N O N - S T E R O I D A L A N T I - I N F L A M M ATO R Y D R U G S ) Selective COX 1 Inhibitors Selective COX 2 Inhibitor Specific COX 2 inhibitors : “COXIB” GAPIPRANT (GALLIPRANT) EP4 receptor antagonist CARPROFEN Weak COX INHIBITOR COX 2 > COX 1 N S A I D s ( N O N - S T E R O I D A L A N T I - I N F L A M M ATO R Y D R U G S ) When? Pre-op or -intra-op? ≠ reaction to ≠ NSAIDs possible Washout period (7-14 days ??) Blood works + urine analysis before/ during treatment Constant monitoring Lean body weight dose Pair with food (some exceptions) Lowest effective dose if long term administration/ administration every other day PA R A C E TA M O L ( A C E TA M I N O P H E N ) COX-3 inhibition (brain): antipyretic effect Acute & Chronic Pain Weak analgesic & anti-inflammatory Licensed (dogs) with codeine for up to 5 days Analgesic mechanism of action? Prostaglandins inhibition Serotoninergic pathway activation Endocannabinoids enhancement L arginine/NO pathway Opioid Mu receptor agonist Use with NSAIDs or Corticosteroids??  ANTI-NERVE GROWTH FACTOR MONOCLONAL ANTIBODIES Frunevetmab (cats), Bedinvetmab (dogs) Inhibition of NGF mediated cell signalling to reduce pain Monthly subcutaneous injection Only licenced for treatment of PAIN associated with OA Contraindicated with NSAIDs (In humans) Allergic reaction, injection site reactions (dermatitis, alopecia, pruritus) Safety with long term exposure & other medication? GABAPENTIN & PREGABALIN  Neuropathic pain/ seizures Acute pain?? Blockage of Ca2+ channels presynaptic neurons →↓ Ca2+ influx→ ↓ excitatory neurotransmitters Use in association with NSAIDs, opioids… Side effects: Sedation, ataxia, vomiting, diarrhoea, increased appetite? A M A N TA D I N E Antagonist of N-methyl-D-aspartate (NMDA) receptors: blockage of pain transmission Decrease central sensitization: long onset of action Chronic pain (in association with other analgesic drugs) Side effects: lethargy, gastro-intestinal upset, seizures Image from: https://psychscenehub.com/psychinsights/memantine- psychopharmacology/ NON-PHARMACOLOGICAL THERAPIES ACUPUNCTURE Image from: https://www.lierre.ca/blogs/acupuncture- supplies/the-ultimate-anatomy-of-acupuncture-needles- guide-presented-by-lierre-ca In association with pharmacological treatment Might help to decrease amount of analgesic drugs needed  older/sicker patients NON-PHARMACOLOGICAL THERAPIES ACUPUNCTURE Insertion of small, flexible needles (acupuncture needles) in specific areas of the bodies (acupoints) Traditional Chinese Medicine/ Western Medicine Mechanism(s) of action? Endorphines release Wound healing Immuno-modulation Modulation of descending inhibitory pathways Gate Control Theory NON-PHARMACOLOGICAL THERAPIES Effects of an acupuncture session NON-PHARMACOLOGICAL THERAPIES PHYSIOTHERAPY:  Hot/cold therapy  Laser therapy  TENS  Massage  Hydrotherapy  Underwater Treadmill NON-PHARMACOLOGICAL THERAPIES ICE THERAPY Decrease in transmission of painful stimuli from periphery and spinal cord Decrease inflammation Decrease tissue metabolism and O2 demand Acute/ inflammatory pain  HOT THERAPY Muscle spasm relieve Stiffness of joints (arthritis..) Improve blood circulation Do not use if acute inflammation is present Chronic pain  NON-PHARMACOLOGICAL THERAPIES LASER (Light Amplification by Stimulated Emission of Radiation) therapy Red-infrared laser light on tissues Photochemical effect (not thermal) Image from: https://thrivehealthsystems.com/class-iv-laser/ NON-PHARMACOLOGICAL THERAPIES LASER THERAPY Video courtesy of Dr. Loris Barale NON-PHARMACOLOGICAL THERAPIES TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION (TENS) Low-voltage electric currents to treat pain & inflammation Gate control theory Endorphins release SUMMARY AAHA Pain Management Guidelines Image from: Gruen ME, Lascelles BDX, Colleran E, Gottlieb A, Johnson J, Lotsikas P, Marcellin-Little D, Wright B. 2022 AAHA Pain Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2022 Mar 1;58(2):55-76. doi: 10.5326/JAAHA-MS-7292. PMID: 35195712. CASE DISCUSSION: CLEMENTINE Clementine is a one-year-old female cat, having an ovariohysterectomy. How would you incorporate analgesia in her anaesthetic protocol? CASE DISCUSSION: FLORENCE Florence needs to have surgery for a fracture repair at the level of the tibia. How would you incorporate analgesia in her anaesthetic protocol? CASE DISCUSSION: BEAR Bear is an 8-year-old male neutered Bernese Mountain dog that has osteoarthritis. He is not on any medication. What would you do to provide pain relief? REFERENCES Taylor S, Gruen M, KuKanich K, et al. 2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery. 2024;26(4). doi:10.1177/1098612X241241951 Gruen ME, Lascelles BDX, Colleran E, Gottlieb A, Johnson J, Lotsikas P, Marcellin-Little D, Wright B. 2022 AAHA Pain Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2022 Mar 1;58(2):55-76. doi: 10.5326/JAAHA-MS-7292. PMID: 35195712. Monteiro, B.P., Lascelles, B.D.X., Murrell, J., Robertson, S., Steagall, P.V.M. and Wright, B. (2023), 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract, 64: 177-254. https://doi.org/10.1111/jsap.13566 THANK YOU FOR YOUR AT T E N T I O N ! ANY QUESTIONS?