ReviewPain mechanisms and their implication for the management of pain in farm and companion animals
Introduction
Pain has been defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP, 1979). However, this definition relies heavily on self-report and language and is therefore of limited use in non-verbal humans and animals (Anand and Craig, 1996). There is no standard, universally accepted scientific definition of pain in animals. For the purpose of this review we use the working definition proposed by Molony (1997) that defines pain as “an aversive sensory and emotional experience representing an awareness by the animal of damage or threat to the integrity of its tissues. It changes the animal’s physiology and behaviour to reduce or avoid the damage, to reduce the likelihood of recurrence and to promote recovery”. Acute (nociceptive) pain serves a protective function and represents an adaptive response to damaging or potentially damaging stimuli. Of particular interest for the veterinary profession is the issue of non-functional (non-useful) pain that occurs “when the intensity or duration of the experience is not appropriate for damage sustained (especially if none exists) and when physiological and behavioural responses are unsuccessful in alleviating it” (Molony, 1997).
Pain is a complex phenomenon, with sensory, cognitive and affective components. Unmitigated pain is associated with suffering, distress and detrimental effects in physical health, representing a welfare concern for practitioners (Hellebrekers, 2000). Pathological pain states are caused mainly by tissue or nerve damage, inflammation, viral infection or demyelination and are characterized by pain hypersensitivity. Inflammatory pain generally responds to anti-inflammatory drugs, but neuropathic pain (due to nerve damage or neural dysfunction) responds poorly to non-steroidal anti-inflammatory drugs (NSAIDs) and is often resistant to opiates (Woolf and Mannion, 1999). Neuropathic pain is clinically manifest as allodynia, hyperalgesia and spontaneous pain (Woolf and Mannion, 1999). Allodynia is defined as pain resulting from normally innocuous stimuli e.g. light touch, while hyperalgesia is defined as an excessive response to painful stimuli (Basbaum and Jessell, 2000).
Studies investigating the epidemiology of pain in domestic animals are limited. However, recently Muir et al., 2004, Wiese et al., 2005 have found that although the most frequently identified type of pain was acute and inflammatory, an incidence of secondary hyperalgesia of 12–18% suggested that central plasticity and sustained pain may be key clinical concerns that should be explored and targeted. Similarly, there is evidence that lame cattle are in a chronic state of hyperalgesia (Whay et al., 1998).
Pre-emptive analgesia (that is, an analgesic treatment administered before the onset of pain) may be important in the prevention of chronic pain as it not only aims to reduce nociception but also sensitisation induced by tissue damage. This phenomenon has been successfully observed in animals following administration of both opioids and NSAIDs (Lascelles, 2000), although its benefits are still debated in human studies (Furlan et al., 2006, Møiniche et al., 2002). The complexity of the mechanisms involved in chronic pain states suggests the need to use multimodal analgesic therapies whereby co-administration of multiple drugs, acting on different receptor targets could result in analgesic synergy and fewer adverse effects.
Section snippets
Neurophysiology of nociception
The neurophysiological processes involved in detection, transduction and transmission of noxious information by nerves and their relay to the central nervous system (CNS) appears essentially similar in all mammals. However, individual variation in pain sensitivity and response to analgesics within species has been identified. The genetic basis of individual variation is being gradually teased out and studies in rodent populations have identified substantial heritable differences in both
Peripheral targets for analgesic agents
Sensory neurons are a primary location for targeting specific molecules involved in nociception. These include inflammatory mediators, growth factors, transducer proteins, ion channels and neuropeptides (such as substance P) whose expression is differentially modified following inflammation or nerve injury. Local anaesthetics such as lidocaine and NSAIDs are currently the main drugs used clinically which act at the periphery, although there is evidence to suggest that opioids may also act at
Management of pain in dogs and cats
As individuals we understand the negative impact of pain on our lives and expect it to be treated effectively: as veterinary surgeons we have a moral, ethical and medical obligation to treat pain in animals under our care. However, we still struggle to free ourselves from the atavistic belief that pain and suffering may be an integral part of life (Caton, 1994). This belief almost certainly influences the attitudes of veterinary surgeons to pain and analgesia in dogs and cats.
Pain is a complex,
Management of pain in farm animals
Pain in farm animals has been traditionally overlooked due, amongst other factors, to the attitudes (and misconceptions) of farmers and veterinary practitioners (Clements et al., 2001, Huxley and Whay, 2006, O’Callaghan, 2002), and also to economic considerations. It has been suggested that prey species might not react overtly to pain stimuli as part of their evolutionary strategy (see, for example, Bateson, 1991). The apparent contrast in pain responses between prey and predator species may
Management of pain in horses
Although the veterinary profession has made considerable progress in assessing pain and providing analgesia for horses, the clinical assessment of pain for this species remains problematic (Raekallio et al., 1997b), with assessment of physiological parameters such as heart rate, behaviour and demeanour used by veterinary surgeons to score clinical pain (Price et al., 2002).
Increases in heart rate can be associated with acute pain in many species (Dobromylskyj et al., 2000, Hardie, 2000, Sanford
Conclusion
Veterinarians have the responsibility of trying to successfully alleviate pain in the animals under their care, but this is goal is limited by the difficulties associated with the identification and measurement of pain in animals and by the relatively narrow range of treatment strategies currently used by veterinarians.
Analgesic treatments should not interfere with normal nociceptive processing, but rather target pain sensitisation specifically. The chronic hypersensitive pain state is
Acknowledgement
I V-F is supported by the British Veterinary Association-Animal Welfare Fund and a post-graduate studentship from the Royal (Dick) School of Veterinary Studies. EJ is supported by the International League for the Protection of Horses (ILPH). Thanks to Vincet Molony for helpful discussions.
References (186)
- et al.
Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain
Pain
(1988) Assessment of pain in animals
Animal Behaviour
(1991)- et al.
Maternal stress differently alters nociceptive behaviors in the formalin test in adult female and male rats
Brain Research
(2003) - et al.
Quantitative assessment of tactile allodynia in the rat paw
Journal of Neuroscience Methods
(1994) - et al.
NMDA receptor antagonists as analgesics: focus on the NR2B subtype
Trends in Pharmacological Sciences
(2001) - et al.
A thermal threshold testing device for evaluation of analgesics in cats
Research in Veterinary Science
(2002) - et al.
Pain assessment
- et al.
Up-regulation of metabotropic glutamate receptor subtypes 3 and 5 in spinal cord in a clinical model of persistent inflammation and hyperalgesia
Pain
(2003) - et al.
The effects of ovariohysterectomy plus different combinations of halothane anaesthesia and butorphanol analgesia on behaviour in the bitch
Research in Veterinary Science
(2000) - et al.
Neuropathic sensitization of behavioral reflexes and spinal NMDA receptor/CaM kinase II interactions are disrupted in PSD-95 mutant mice
Current Biology
(2003)
Nociception in vertebrates: key receptors participating in spinal mechanisms of chronic pain in animals
Brain Research Reviews
Assessment of the influence of surgical technique on postoperative pain and wound tenderness in cats following ovariohysterectomy
Journal of Feline Medicine and Surgery
Behavior after ovariohysterectomy in the dog: what’s normal?
Applied Animal behaviour Science
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Pain
Assessment of pain induced by castration in piglets: behavioural and physiological responses over the subsequent 5 days
Applied Animal Behaviour Science
Novel class of pain drugs based on antagonism of NFG
Trends in Pharmacological Sciences
NK1 (substance P) receptor antagonists – why are they not analgesic in humans?
Trends in Pharmacological Sciences
Messenger plasticity in primary sensory neurons following axotomy and its functional implications
Trends in Neuroscience
Attitudes and concerns of French veterinarians towards pain and analgesia in dogs and cats
Veterinary Anaesthesia and Analgesia
The relationship between tail biting in pigs, docking procedure and other management practices
The Veterinary Journal
Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain
Neurobiology of Disease
A method for studying cutaneous pain perception and analgesia in horses
Journal of Pharmacological Methods
Mechanisms of inflammatory pain
British Journal of Anaesthesia
Comparison of transdermal fentanyl and intramuscular oxymorphone on post-operative behavior after ovariohysterectomy in dogs
Research in Veterinary Science
Attenuation of negative pain affect produced by unilateral spinal nerve injury in the rat following anterior cingulate cortex activation
Neuroscience
Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy
Pain
Pain, plasticity, and premature birth: a prescription for permanent suffering?
Nature Medicine
New perspectives on the definition of pain
Pain
Challenges of pain assessment in domestic animals
Journal of the American Veterinary Medical Association
Pain detection and amelioration in animals on the farm: issues and options
Journal of Applied Animal Welfare Science
Behavioural assessment of pain in horses and donkeys: application to clinical practice and future studies
Equine Veterinary Journal
Use of anticonvulsants for treatment of neuropathic pain
Neurology
The perception of pain
Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli
Journal of Neurophysiology
Chronic pain, chronic stress and depression: coincidence or consequence?
Journal of Neuroendocrinology
Effect of carprofen, etodolac, meloxicam or butorphanol in dogs with induced acute synovitis
American Journal of Veterinary Research
Limb movement adaptations in horses with experimentally induced fore- or hindlimb lameness
Equine Veterinary Journal
Long-term temporal evaluation of ground reaction forces during development of experimentally induced osteoarthritis in dogs
American Journal of Veterinary Research
Heart rate variability is related to pain severity and predominant bowel pattern in women with irritable bowel syndrome
Neurogastroenterology and Motility
Subjective and objective measurements of post-operative pain in cats
Journal of the American Medical Association
Current British veterinary attitudes to perioperative analgesia for dogs
The Veterinary Record
Recent developments in Nonsteroidal anti-inflammatory drugs in cats
Journal of the American Animal Hospital Association
Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats
Journal of the American Veterinary Medical Association
Impaired nociception and pain sensation in mice lacking the capsaicin receptor
Science
“The poem in the pain”. The social significance of pain in western civilization
Anesthesiology
Electrophysiological characterization of spinal neuronal response properties in anaesthetized rats after ligation of spinal nerves L5–L6
Journal of Physiology
Reporting of sheep lameness conditions to veterinarians in the Scottish Borders
The Veterinary Record
The contribution of excitatory amino acids to central sensitisation and persistent nociception after formalin-induced tissue injury
Journal of Neuroscience
Correlation between subjective and objective measures used to determine severity of post-operative pain in dogs
Journal of the American Veterinary Medical Association
Evaluation of a canine total-elbow arthroplasty system: a preliminary study in normal dogs
Veterinary Surgery
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