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Monitoring and treating chronic pain in cats: bring on the challenge!
The Veterinary Journal 196 (2013) 275–276
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Monitoring and treating chronic pain in cats: Bring on the challenge! In contrast to acute pain conditions, chronic pain in the cat is relatively poorly identified. Osteoarthritis (OA) is very common in older cats. However, we currently lack validated clinical tools to diagnose and quantify chronic OA-related pain in feline practice and, consequently, to monitor the effects of analgesic treatments. The assessment of pain is challenging because of (1) the general demeanour of the cat; (2) the uncertainty of what actually constitutes chronic pain, both in spontaneously occurring clinical situations and experimental models; and (3) the validity of equipment and observational methods developed to monitor chronic pain in this species. Pain is a psychological state comprising three recognised dimensions; the experience of pain evokes physical sensations, as well as psychological experiences. While the ‘sensory-discriminative’ component (intensity, location and duration of the pain) can be objectively characterised and quantified in animals, the unavoidable lack of self-reporting precludes exploration of the second and third components, the ‘affective–motivational’ (emotional and aversive aspects of pain) and ‘cognitive–evaluative’ (evaluation of consequences of pain upon quality of life) dimensions. At best, these can be extrapolated only from owner’s perception and understanding of their pet’s quality of life. The classic experimental approach for evaluation of treatments for chronic pain is challenged by the observation that analgesic development programmes based on rodent experimental pain models have usually failed to predict good clinical efficacy and margin of safety during subsequent assessment in man (Lascelles and Flecknell, 2010). Even if an ethical experimental model of OA-related chronic pain was validated in the cat, it might have limited clinical relevance, since the intensity and time course of development of the chronic pain state, as well as the underlying molecular mechanisms involved in central sensitisation, are likely to differ from pain secondary to clinical OA that develops spontaneously over relatively long periods of time. Since osteoarthritis pathophysiology and its clinical picture in dogs are considered to be similar to the human disease, Vainio (2012) has promoted the study of OA in canine patients as a valuable translational model, not only to convert basic scientific advances into clinical practice, but also to study OA-related pain in humans. The translational leap of faith from clinically affected dog to clinically affected human is less speculative than experimental rodent to clinically affected human. To date, subjective measures (owner-completed questionnaires) and objective measures (gait analysis) of OA-related pain have been validated in dogs, but not in cats (Vainio, 2012). This issue of The Veterinary Journal includes two feline studies, both carried out in feline populations with naturally occurring OA-related pain to validate two complementary approaches, providing subjective (Benito et al., 2013) and objective (Guillot et al.,
1090-0233/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2013.04.006
2013) measures of OA-related pain. Drs. Javier Benito, Duncan Lascelles and colleagues, at North Carolina State University, USA, recruited client-owned cats to validate a Feline Musculoskeletal Pain Index (FMPI) based on subjective assessment by a proxy (owner) in the animals’ natural environment, away from the stress of the consultation room (Benito et al., 2013). Their approach takes into account activity criteria, probing 17 activities, leading to an overall activity score, as well as overall pain and quality of life by the owners. In the same issue, Drs. Martin Guillot, Eric Troncy and colleagues, at the Université de Montréal, Canada, studied a population of laboratory cats with spontaneously occurring degenerative joint disease (Guillot et al., 2013). They related the magnitude of and changes in three objective criteria in relation to feline OA-related pain: (1) peak vertical ground reaction forces; (2) accelerometer-based motor activity; and (3) the pressure required to elicit paw withdrawal after stimulation with a Von Frey anaesthesiometer (in an attempt to encompass an allodynic component). In both studies, the definition of precise clinical and radiographic inclusion criteria for the unequivocal selection of OA pain-affected and control cats was of paramount importance, especially given the high prevalence of radiographic lesions in the ageing cat and the poor correlation between pain elicited on palpation/manipulation and radiographic evidence of OA (Lascelles et al., 2012). Clinical relevance is essential if these methods are to be adopted to standardise the daily assessment of feline pain. Great care was taken by Benito et al. (2013) to ensure clear readability of the FMPI and accuracy in practical use by owners. It seems unlikely that study of peak vertical force and Von Frey analgesiometry would routinely translate into non-referral clinics, due to the time and capital investment required. However, the accelerometry-based technology has promising potential for monitoring changes in motor activity. Advantages are its lightweight construction, allowing day/night continuous activity recording, and the interest of several companies, who are in the process of developing easy-to-use and more affordable commercial versions. Non-steroidal anti-inflammatory drugs (NSAIDs) provide the therapeutic basis for long term management of chronic pain associated with osteoarthritis. There is a wealth of data on the efficacy and safety of these therapeutic agents, in the peer reviewed literature, as well as submitted to regulatory authorities during the registration process. However, meloxicam is the only NSAID officially licensed for chronic use in the cat (in Europe only). Other analgesics or adjuvants, such as opioids (oraltransmucosal buprenorphine, tramadol), gabapentin, amantadine (N-methyl-D-aspartate (NMDA) receptor blocker) and antidepressants are also used, usually in conjunction with NSAIDs for chronic pain, as well as non-pharmacological approaches (Grubb, 2010).
276
Guest Editorial / The Veterinary Journal 196 (2013) 275–276
Cyclooxygenase (COX)-2 selective NSAIDs have the potential to provide improved gastrointestinal tolerance when used long term in the cat due to their COX-1 sparing effect. However, with currently available knowledge, it is unclear whether their use represents a significant improvement for renal safety compared to non-selective or even COX-1 selective NSAIDs, especially in the elderly feline population. To minimise potential side effects with chronic use of NSAIDs, recent consensus guidelines on their long term use in cats recommend an individualised dose titration to the ‘lowest effective dose’ to provide satisfactory analgesia (Sparkes et al., 2010). Validated pain assessment tools, such as those published in this issue, have long been needed to reliably inform clinical decisions to maintain or alter the dosage regimen and to support prospective analgesia efficacy studies in feline chronic pain. However, further clinical validation is required to explore the discrimination abilities of these tools for evaluating subtle changes in lameness and pain when a cat is presented after an interval of a few weeks and to exclude the effects of temporal owner-related bias, as owners become proficient at identifying painrelated behaviour in their pets.
Ludovic Pelligand Department of Comparative Biomedical Sciences, Royal Veterinary College, United Kingdom E-mail address: [email protected] PeterLees Emeritus Professor Royal Veterinary College, United Kingdom E-mail address: [email protected]
References Benito, J., Depuy, V., Hardie, E., Zamprogno, H., Thomson, A., Simpson, W., Roe, S., Hansen, B., Lascelles, B.D., 2013. Reliability and discriminatory testing of a client-based metrology instrument, feline musculoskeletal pain index (FMPI) for the evaluation of degenerative joint disease-associated pain in cats. The Veterinary Journal 196, 368–373. Grubb, T., 2010. What do we really know about the drugs we use to treat chronic pain? Topics in Companion Animal Medicine 25, 10–19. Guillot, M., Moreau, M., Heit, M., Martel-Pelletier, J., Pelletier, J.P., Troncy, E., 2013. Characterization of osteoarthritis in cats and meloxicam efficacy using objective chronic pain evaluation tools. The Veterinary Journal 196, 360–367. Lascelles, B.D., Flecknell, P., 2010. Do animal models tell us about human pain. Pain: Clinical Updates 18, 1–6. Lascelles, B.D., Dong, Y.H., Marcellin-Little, D.J., Thomson, A., Wheeler, S., Correa, M., 2012. Relationship of orthopedic examination, goniometric measurements, and radiographic signs of degenerative joint disease in cats. BMC Veterinary Research 8, 10. Sparkes, A.H., Heiene, R., Lascelles, B.D., Malik, R., Sampietro, L.R., Robertson, S., Scherk, M., Taylor, P., 2010. ISFM and AAFP consensus guidelines: Long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery 12, 521–538. Vainio, O., 2012. Translational animal models using veterinary patients: An example of canine osteoarthritis (OA). Scandinavian Journal of Pain 3, 84–89.
Contents lists available at SciVerse ScienceDirect
The Veterinary Journal journal homepage: www.elsevier.com/locate/tvjl
Guest Editorial
Monitoring and treating chronic pain in cats: Bring on the challenge! In contrast to acute pain conditions, chronic pain in the cat is relatively poorly identified. Osteoarthritis (OA) is very common in older cats. However, we currently lack validated clinical tools to diagnose and quantify chronic OA-related pain in feline practice and, consequently, to monitor the effects of analgesic treatments. The assessment of pain is challenging because of (1) the general demeanour of the cat; (2) the uncertainty of what actually constitutes chronic pain, both in spontaneously occurring clinical situations and experimental models; and (3) the validity of equipment and observational methods developed to monitor chronic pain in this species. Pain is a psychological state comprising three recognised dimensions; the experience of pain evokes physical sensations, as well as psychological experiences. While the ‘sensory-discriminative’ component (intensity, location and duration of the pain) can be objectively characterised and quantified in animals, the unavoidable lack of self-reporting precludes exploration of the second and third components, the ‘affective–motivational’ (emotional and aversive aspects of pain) and ‘cognitive–evaluative’ (evaluation of consequences of pain upon quality of life) dimensions. At best, these can be extrapolated only from owner’s perception and understanding of their pet’s quality of life. The classic experimental approach for evaluation of treatments for chronic pain is challenged by the observation that analgesic development programmes based on rodent experimental pain models have usually failed to predict good clinical efficacy and margin of safety during subsequent assessment in man (Lascelles and Flecknell, 2010). Even if an ethical experimental model of OA-related chronic pain was validated in the cat, it might have limited clinical relevance, since the intensity and time course of development of the chronic pain state, as well as the underlying molecular mechanisms involved in central sensitisation, are likely to differ from pain secondary to clinical OA that develops spontaneously over relatively long periods of time. Since osteoarthritis pathophysiology and its clinical picture in dogs are considered to be similar to the human disease, Vainio (2012) has promoted the study of OA in canine patients as a valuable translational model, not only to convert basic scientific advances into clinical practice, but also to study OA-related pain in humans. The translational leap of faith from clinically affected dog to clinically affected human is less speculative than experimental rodent to clinically affected human. To date, subjective measures (owner-completed questionnaires) and objective measures (gait analysis) of OA-related pain have been validated in dogs, but not in cats (Vainio, 2012). This issue of The Veterinary Journal includes two feline studies, both carried out in feline populations with naturally occurring OA-related pain to validate two complementary approaches, providing subjective (Benito et al., 2013) and objective (Guillot et al.,
1090-0233/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tvjl.2013.04.006
2013) measures of OA-related pain. Drs. Javier Benito, Duncan Lascelles and colleagues, at North Carolina State University, USA, recruited client-owned cats to validate a Feline Musculoskeletal Pain Index (FMPI) based on subjective assessment by a proxy (owner) in the animals’ natural environment, away from the stress of the consultation room (Benito et al., 2013). Their approach takes into account activity criteria, probing 17 activities, leading to an overall activity score, as well as overall pain and quality of life by the owners. In the same issue, Drs. Martin Guillot, Eric Troncy and colleagues, at the Université de Montréal, Canada, studied a population of laboratory cats with spontaneously occurring degenerative joint disease (Guillot et al., 2013). They related the magnitude of and changes in three objective criteria in relation to feline OA-related pain: (1) peak vertical ground reaction forces; (2) accelerometer-based motor activity; and (3) the pressure required to elicit paw withdrawal after stimulation with a Von Frey anaesthesiometer (in an attempt to encompass an allodynic component). In both studies, the definition of precise clinical and radiographic inclusion criteria for the unequivocal selection of OA pain-affected and control cats was of paramount importance, especially given the high prevalence of radiographic lesions in the ageing cat and the poor correlation between pain elicited on palpation/manipulation and radiographic evidence of OA (Lascelles et al., 2012). Clinical relevance is essential if these methods are to be adopted to standardise the daily assessment of feline pain. Great care was taken by Benito et al. (2013) to ensure clear readability of the FMPI and accuracy in practical use by owners. It seems unlikely that study of peak vertical force and Von Frey analgesiometry would routinely translate into non-referral clinics, due to the time and capital investment required. However, the accelerometry-based technology has promising potential for monitoring changes in motor activity. Advantages are its lightweight construction, allowing day/night continuous activity recording, and the interest of several companies, who are in the process of developing easy-to-use and more affordable commercial versions. Non-steroidal anti-inflammatory drugs (NSAIDs) provide the therapeutic basis for long term management of chronic pain associated with osteoarthritis. There is a wealth of data on the efficacy and safety of these therapeutic agents, in the peer reviewed literature, as well as submitted to regulatory authorities during the registration process. However, meloxicam is the only NSAID officially licensed for chronic use in the cat (in Europe only). Other analgesics or adjuvants, such as opioids (oraltransmucosal buprenorphine, tramadol), gabapentin, amantadine (N-methyl-D-aspartate (NMDA) receptor blocker) and antidepressants are also used, usually in conjunction with NSAIDs for chronic pain, as well as non-pharmacological approaches (Grubb, 2010).
276
Guest Editorial / The Veterinary Journal 196 (2013) 275–276
Cyclooxygenase (COX)-2 selective NSAIDs have the potential to provide improved gastrointestinal tolerance when used long term in the cat due to their COX-1 sparing effect. However, with currently available knowledge, it is unclear whether their use represents a significant improvement for renal safety compared to non-selective or even COX-1 selective NSAIDs, especially in the elderly feline population. To minimise potential side effects with chronic use of NSAIDs, recent consensus guidelines on their long term use in cats recommend an individualised dose titration to the ‘lowest effective dose’ to provide satisfactory analgesia (Sparkes et al., 2010). Validated pain assessment tools, such as those published in this issue, have long been needed to reliably inform clinical decisions to maintain or alter the dosage regimen and to support prospective analgesia efficacy studies in feline chronic pain. However, further clinical validation is required to explore the discrimination abilities of these tools for evaluating subtle changes in lameness and pain when a cat is presented after an interval of a few weeks and to exclude the effects of temporal owner-related bias, as owners become proficient at identifying painrelated behaviour in their pets.
Ludovic Pelligand Department of Comparative Biomedical Sciences, Royal Veterinary College, United Kingdom E-mail address: [email protected] PeterLees Emeritus Professor Royal Veterinary College, United Kingdom E-mail address: [email protected]
References Benito, J., Depuy, V., Hardie, E., Zamprogno, H., Thomson, A., Simpson, W., Roe, S., Hansen, B., Lascelles, B.D., 2013. Reliability and discriminatory testing of a client-based metrology instrument, feline musculoskeletal pain index (FMPI) for the evaluation of degenerative joint disease-associated pain in cats. The Veterinary Journal 196, 368–373. Grubb, T., 2010. What do we really know about the drugs we use to treat chronic pain? Topics in Companion Animal Medicine 25, 10–19. Guillot, M., Moreau, M., Heit, M., Martel-Pelletier, J., Pelletier, J.P., Troncy, E., 2013. Characterization of osteoarthritis in cats and meloxicam efficacy using objective chronic pain evaluation tools. The Veterinary Journal 196, 360–367. Lascelles, B.D., Flecknell, P., 2010. Do animal models tell us about human pain. Pain: Clinical Updates 18, 1–6. Lascelles, B.D., Dong, Y.H., Marcellin-Little, D.J., Thomson, A., Wheeler, S., Correa, M., 2012. Relationship of orthopedic examination, goniometric measurements, and radiographic signs of degenerative joint disease in cats. BMC Veterinary Research 8, 10. Sparkes, A.H., Heiene, R., Lascelles, B.D., Malik, R., Sampietro, L.R., Robertson, S., Scherk, M., Taylor, P., 2010. ISFM and AAFP consensus guidelines: Long-term use of NSAIDs in cats. Journal of Feline Medicine and Surgery 12, 521–538. Vainio, O., 2012. Translational animal models using veterinary patients: An example of canine osteoarthritis (OA). Scandinavian Journal of Pain 3, 84–89.