Recognising and managing pain in small mammals and exotics
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1 Vet Times The website for the veterinary profession Recognising and managing pain in small mammals and exotics Author : Elisabetta Mancinelli Categories : RVNs Date : November 1, 2011 Elisabetta Mancinelli CertZooMed, MRCVS, looks at how certain species cope with pain and how it can be managed Summary PAINmay be described as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Veterinarians dealing with exotic animals must be aware all species might experience pain. Recognising signs of pain and its severity can be challenging, especially in prey species. Furthermore it is still controversial whether rabbits, rodents, birds, reptiles and fish perceive pain with the same intensity. It can be even more difficult to objectively determine if a given medication is effective in alleviating pain in exotic animals. The lack of familiarity with certain drugs and their use in different species can complicate things further. It is now widely recognised that providing adequate analgesia, as part of a treatment plan for many medical or surgical conditions, is essential to be able to give the appropriate care and meet a patient s needs. Key words pain management, mortality, exotic animals, analgesia, noxious stimuli IMPROVEMENTS during the past 20 years in the provision of medical and surgical care for exotic pets has resulted in a healthier and longer life for many of these animals. Many 1 / 7
2 owners are dedicated to providing excellent care for their pets and the veterinarian involved also needs to be aware of anatomical, physiological and behavioural peculiarities, so that when a patient is presented for a health problem, the appropriate and specific treatments are provided. Pain recognition and management across different exotic species is one of the biggest challenges faced by a clinician in daily practice. Defining pain Pain can be associated with many diseases and trauma ( Figure 1 ), and as a result of surgical interventions. It has been defined as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage 1. It is important to stress many studies suggest that psychological stress can negatively affect an animal s welfare and quality of life as much as physical pain can 2. It is generally accepted that any procedure or disease likely to cause pain in human beings, should be expected to cause pain in an animal 3, 4. Pain control is necessary whether treating painful conditions such as gastrointestinal (GI) stasis, dental disease, trauma, burns or fractures or simply premedicating an animal prior to a procedure likely to cause pain. As a result, analgesics should be part of any anaesthetic protocol. Our patients will greatly benefit from judicious use of analgesic agents. To be able to alleviate pain, one must first be able to recognise it, to assess its intensity and identify its source and duration. It may be difficult to confirm if an animal is in pain, because animals cannot express their pain verbally. Different species will have different behavioural responses to noxious stimuli, and individual differences in pain tolerance 5 must also be considered. Moreover, exhibiting normal behaviour is not necessarily an indication that an animal is not in pain. Therefore, the recognition of pain is often based on experience, familiarity with the different species and their normal behaviour and the professional judgement of the clinician 3. Prey species, such as rabbits, rodents and birds, tend to mask symptoms of disease, especially in an unusual environment. They may freeze during examination, making recognising clinical signs of pain even more difficult. Daytime observation of species that are mainly active at night, such as rats and hamsters, may lead to inaccurate interpretation of their behaviour 6. Acute traumatic or postoperative pain may induce immobility in rabbits, ferrets and birds. These animals may be profoundly depressed, with their eyes half-closed or shut, not grooming themselves and avoiding attention and isolating themselves from other animals. Bruxism may be seen in rabbits, rodents and ferrets. Abnormal body position, such as a hunched posture and abdominal pressing or change in temperament, has also been described in association with pain 5. Guinea pigs tend to squeal even when handled normally but, if in pain, may remain silent, change their facial expression and become more aggressive 7. Some animals in pain may chew, lick, bite or excessively groom at the site of pain. Birds in pain may hide, be reluctant to perch ( Figure 2 ) and may start feather picking, plucking or create skin wounds over a specific body area 5. 2 / 7
3 Changes in skin colour have been attributed to pain in amphibians and reptiles. Opinion differs on whether reptiles have nervous structures capable of processing noxious stimuli (which could mean they just show passive reflexive responses to them) or they are actually able to consciously feel pain in the same way and intensity as other animals 8, 9. It has been assumed for years that the capacity to feel pain may decrease with phylogenetic position from Mammalia to fish 10. Research in fish, reptiles, amphibians and birds has demonstrated that areas in these animals forebrains can receive sensory signals and might be homologous to the limbic and cortical areas of mammalian species 9. We should, therefore, consider that what is painful for humans and mammals is also painful for other non-mammalian vertebrate species ( Figure 3 ). Many pain-scoring methods have been evaluated over the years. Physiological parameters such as heart and respiratory rate, blood pressure, plasma cortisol/corticosterone and/or catecholamine concentrations have sometimes been used to assess pain in humans and other species. Many factors, although not pain related, can influence these parameters 11. It has also been suggested that the same parameters used to indicate stress may be used to assess pain. In birds, for example, corticosteroids (well-known humoral indicators of stress) have been evaluated as indicators of acute pain, but areb considered unreliable as they can increase simply with handling 12, 13. Rodents have often been used in biomedical research as a model for assessing pain by applying thermal noxious stimuli 14. Limb or tail withdrawal latency, after application of a noxious stimulus, is the method often used to assess pain in reptiles 15, 16. Evaluation of behaviour, respiration rate, heart rate, bodyweight, food and water consumption and the return of normal behaviour and movement are commonly used to evaluate animals and are often used postoperatively (with and without analgesia), to measure nociception and analgesia in various species 5. It can be concluded that there is no objective and universally applicable way to assess and classify pain in animals. This remains a very complex process and one that is often based on the clinical impression of the animal. Pain management Pain can delay healing, lower immune responses and increase morbidity and mortality 17. Appropriate analgesia is, therefore, expected to allow more rapid return to a normal behaviour in mammals 18. The process of nociception (processing noxious stimuli) involves different levels and pathways; therefore, an optimal pain management plan involves the use of multiple drugs, acting at different levels (multimodal analgesia). Smaller doses of each can be used, thereby enhancing pain relief and reducing the likelihood of side effects 19, 4. For example, an opioid could be used to premedicate a ferret, rabbit or rodent undergoing surgery, to modulate pain. A local anaesthetic block may be used to inhibit pain transmission and an NSAID could be administered perioperatively 3 / 7
4 to alter pain transduction. Evidence also suggests recovery can be hastened if opioids, NSAIDs and local anaesthetics are used to pre-emptively block the sensitisation of the central nervous system (CNS) from a noxious stimulus before the tissue injury occurs (pre-emptive analgesia) 20, 21. For the majority of agents the pain is alleviated after having already been induced (post-inductive) and this is why local anaesthetics are arguably the best analgesics available, as they block pain production at the site of the initial insult. The major classes of analgesic drugs used for managing acute and chronic pain in exotic animal practice include opioids, NSAIDs and local anaesthetics. However, agents such as ketamine and alpha-2 agonists also provide analgesia and are often included in anaesthetic protocols or by lowdose constant-rate infusions during a procedure 4. Selection of the appropriate analgesic protocol should take into account pain physiology and the pharmacokinetic properties of that drug in a particular species 3, 5. Opioids act centrally to limit the arrival of nociceptive information to the CNS. Effects and dosages vary according to species, source and pain type 22 ( Figure 4 ). They are used for their potent and rapidonset action in alleviating moderate to severe acute pain 3, 6. They act by binding to mu, kappa or delta-opoid receptors in the CNS or peripherally in inflamed tissues of mammals 23. Birds have been demonstrated to have mainly kappaopioid receptors, therefore, kappa-opioid agonists (such as butorphanol or tramadol) are more effective for pain management 24. Birds also appear not to respond in the same manner as mammals to mu-opioid receptor agonists 25, 5. Rabbits, ferrets and other small mammals are considered more sensitive to the respiratory and GI side effects of opioids 4. Used at the recommended doses, these drugs have a wide margin of safety and are very effective in alleviating pain. Their use in these species is, therefore, highly desirable as the painful alternative can be even more deleterious 22. Little is known about opioid receptor distribution and function in reptiles 5. Butorphanol is ineffective in bearded dragons and red-eared slider turtles, and data is insufficient regarding snakes. Morphine is considered more effective than kappa-agonists in bearded dragons and turtles, but the data is not clear for corn snakes. Both drugs can also cause severe respiratory depression in turtles 15, 16. Despite some useful pharmacokinetic studies we still do not know the serum levels required for analgesia. Amphibians seem to possess a kappa-like opioid receptor called the unireceptor, which permits binding of mu, kappa and delta agonists to produce adequate analgesia 26. Tramadol is an opiod-type drug that can act by binding to mu-opioid receptors or inhibiting norepinephrine and serotonin uptake. It has been described as inducing effective analgesia in humans, but oral administration of 11mg/kg in rabbits achieved variable plasma levels below those considered analgesic in humans 27. It has been reported that 10mg/kg, once daily is effective for ferrets 4 whereas 5-10mg/kg seems to induce prolonged analgesia in turtles 9. Different dosages have been recommended for bald eagles, red-tailed hawks and Hispaniolan Amazon parrots 28, 29, 30. NSAIDs act peripherally to block nociception and decrease inflammation, thereby limiting the 4 / 7
5 information directed to the CNS. They are generally used to alleviate acute postoperative and traumatic pain ( Figure 5, 6 and 7 ). Their anti-inflammatory and analgesic properties and side effects are due to the inhibition of cyclo-oxygenase (COX) enzyme in the arachidonic acid pathway 5. The main concerns are related to the inhibition of prostaglandin synthesis, which may lead to impaired renal function, GI erosions and bleeding disorders 22. The main advantages of these drugs are their prolonged duration of action and the fact that they are not controlled 4. Carprofen, ketoprofen and meloxicam are safely used for effective pain relief and are well tolerated in rabbits, rodents and birds. Many authors recommend their use in stable normovolaemic animals post-surgery, when they start eating and with normal renal values, in view of possible intra-operative risks of bleeding and hypotension 4. One study, using 0.3mg/kg of meloxicam, showed no changes in physiologic parameters or behaviour in ball pythons 31. The glucuronidation conjugation system (which is required for metabolism) seems to be limited in ferrets 32. This could lead to prolonged activity of some NSAIDs and increased risk of side effects if the dose or the frequency of administration are not calibrated appropriately 22. Local anaesthetics may be administered topically, locally (infiltration of the surgical site), through peripheral nerve blocks or epidurally, to inhibit neural transmission to the CNS. Lidocaine (1-2mg/kg in small mammals) and bupivacaine (1mg/kg) are the most common agents used, with bupivacaine prolonging the potency and duration of the local anaesthesia, but with higher toxic effects 4, 7, 17. The addition of morphine or buprenorphine to the mixture can potentially prolong the duration of the local anaesthesia by 10 and nine hours, respectively 33. Birds are considered more sensitive to the toxic effect of local anaesthetics than mammals 5. Microdoses of alpha-2 agonists, such a medetomidine or dexmedetomidine, can be used in combination with a tranquilliser or an opioid to provide analgesia, along with muscle relaxation and sedation. Used appropriately these agents minimally affect blood pressure and cardiovascular parameters 4. Ketamine is often included in the anaesthetic protocol to reduce pain windup. Microdoses can also be given via a constant-rate infusion, in combination with an opioid, to provide analgesia 22. Finally Last, but not least, it is important to be reminded of the benefits that other therapies can have when used alongside traditional analgesia. Cryotherapy, laser therapy, heat therapy, massage and rehabilitation can help in speeding recovery from trauma or surgery and have fewer adverse effects, when used with awareness 34. Alternative medical therapies, such as acupuncture, are also increasingly being considered to help reduce pain during the treatment of many common medical conditions. The neuromodulation that acupuncture induces (by direct nerve stimulation) can alter pain transmission and aid in pain control and management 35. Good pain management can also be achieved by providing appropriate housing and husbandry practices, in a stress-free environment, with appropriate handling and adequate surgical techniques 3. 5 / 7
6 References 1. International Association for the Study of Pain 2. McMillan F D (2003). A world of hurts, JAVMA 223(2): Kohn D F, Martin T E, Foley P L, et al (2007). Guidelines for the Assessment and Management of Pain in Rodents and Rabbits, J Am Assoc Lab Anim Sci 46: Lichtenberger M, Ko J. (2007). Anaesthesia and Analgesia for Mammals and Birds, Vet Clin of North Am Exot Anim Pract 10: Hawkins M G (2006). The use of analgesics in birds, reptiles and small exotic mammals, Journal of Exotic Pet Medicine 15(3): Flecknell P A (1998). Analgesia in small mammals, Seminars in Avian and Exotic Pet Medicine 7(1): Miller A L, Richardson C A (2011). Rodent analgesia, Vet Clin of North Am Anim Exot Anim Pract 14: Paul-Murphy J, Ludders J W, Robertson S A, et al (2004). The need for a cross-species approach to the study of pain in animals, JAVMA 222: 1,559-1, Sladky K K (2010). Reptile analgesia: is laughter the best medicine for pain? NAVC Conference Proceedings. 10. Stevens C W (1992). Alternatives to the use of mammals for pain research, Life Sci 50: Livingston A, Chambers P (2000). The physiology of pain. In Flecknell P, Waterman- Pearson A, (eds). Pain management in animals, W B Saunders, London Harvey S, Phillips J, Rees A, et al (1984). Stress and adrenal function, J Exp Zool 232: Heatley J J, Oliver J W, Hosgood G, et al (2000). Serum corticosterone in response to restraint, anesthesia and skin testing in Hispaniolan Amazon parrots (Amazona ventralis), J Avian Med Surg 14: Hargreaves K, Dubner R, Brown F, et al (1998). A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia, Pin 32: Sladky K K, Miletic V, Paul-Murphy J, et al (2007). Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles (Trachemys scripta), JAVMA, 230: 1,356-1,362; 16. Sladky K K, Kinney M E, Johnson S M (2008). Analgesic efficacy of buthorphanol and morphine in bearded dragons and corn snakes, JAVMA 233: Barter L S (2011). Rabbit analgesia, Vet Clin of North Am Anim Exot Anim Pract 14: Hardie E M, Hansen B D, Carroll G S (1997). Behaviour after ovariohysterectomy in the dog: what s normal? Appl Anim Behav Sci 51: Fisher P G (2010). Standards of care in the 21st Century: the Rabbit. Journal of Exotic Pet Medicine, 19(1): Katz J, Kavanagh B P, Sandler A N, et al (1992). Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain, Anesthesiology 77: / 7
7 Powered by TCPDF ( 21. Reichert J A, Daughters R S, Rivard R, et al (2001). Peripheral and preemptive opioid antinociception in a mouse visceral pain model, Pain 89: Lichtenberger M, Lennox A M, (2009). Exotic companion mammal emergency medicine and critical care. AEMV Conference Proceedings. 23. Stein C, Lang L J (2009). Peripherl mechanisms of opioid analgesia, Curr Opin Phrmacol, 9(1): Reiner A, Brauth S E, Kitt C A, et al (1989). Distribution of mu, delta and kappa opioid receptor types in the forebrain and midbrain of pigeons, J Comp Neurol 280: Paul-Murphy J, Brunson D B, Miletic V (1999). Analgesic effects of butorphanol and buprenorphine in conscious African grey parrots (Psittacus erithacus erithacus and Psittacus erithacus timneh), Am J Vet Res 60: 1,218-1, Newman L C, Sands S S, Wallace D R, Stevens C W (2002). Characterization of mu, kappa, and delta opioid binding in amphibian all brain tissue homogenates, J Pharmacol Exp Ther 301: Souza M J, Greenacre C B, Cox S K (2008). Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus), Am J Vet Res 69(8): Souza M J, Martin-Jimenez T, Jones M P, et al (2009). Pharmacokinetics of oral and intravenous tramadol in bald eagles, J Avian Med Surg 23: Souza M J, Guzman D S, Paul-Murphy J, et al (2010). Tramadol in Hispaniolam Amazon parrots (Amazona ventralis), Proceedings of the Association of Avian Veterinarians, San Diego (CA), Souza M J, Martin-Jimenez T, Jones M P, et al. Pharmacokinetics of oral tramadol in red-tailed hawks, J Vet Pharm Therap, DOI:10: 1111/j x. 31. Olesen M G, Bertelsen M F, Perry S F, Wang T (2008). Effects of preoperative administration of butorphanol or meloxicam on physiologic responses to surgery in ball pythons, JAVMA 233(12): 1,883-1, Court M H (2001). Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6, J Vet Pharmacol Ther 24: Bazin J E, Massoni C, Bruell P, et al (1997). The addition of opioids to the local anesthetics in brachial plexus block: the comparative effects of morphine, buprenorphine and sufentanil, Anesthesia 52(9): Rychel J K, Robinson N G (2011). Zoological companion animal rehabilitation and physical medicine, Vet Clin of North Am Anim Exot Anim Pract 14: Koski M A (2011). Acupuncture for zoological companion animals, Vet Clin of North Am Anim Exot Anim Pract 14: / 7
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