The refinement of husbandry and procedures to reduce animal suffering and improve welfare is an essential component of humane science. Successful refinement depends upon the ability to assess animal welfare effectively, and detect any signs of pain or distress as rapidly as possible, so that any suffering can be alleviated. This document provides practical guidance on setting up and operating effective protocols for the welfare assessment of animals used in research and testing. It sets out general principles for more objective observation of animals, recognizing and assessing indicators of pain or distress and tailoring these to individual projects. Systems for recording indicators, including score sheets, are reviewed and guidance is set out on determining practical monitoring regimes that are more likely to detect any signs of suffering. This guidance is intended for all staff required to assess or monitor animal welfare, including animal technologists and care staff, veterinarians and scientists. It will also be of use to members of ethics or animal care and use committees. A longer version of this document, with further background information and extra topics including training and information sharing, is available on the Laboratory Animals website.
Rat behaviour was studied to develop a reliable method of determining the severity and duration of post-laparotomy pain, and to assess analgesic effects of ketoprofen or carprofen. Behaviour was studied in groups of ten animals 1 h following subcutaneous (s/c) saline (0.2 ml/100 g), ketoprofen or carprofen (5, 10 or 15 mg/kg) given either alone, or prior to surgery. The frequency of over 150 individual behavioural acts was calculated during the first post-treatment hour, the hour immediately prior to darkness, and the first 15 min of each of 5 subsequent hours. Discriminant analysis and analysis of variance isolated several easily recognizable behaviours which were markedly altered in frequency by surgery. These were unaffected by drug administration alone and were mainly transient, easily quantifiable activities; 'cat-like' back arching, horizontal stretching followed by abdominal writhing and twitching while inactive. Reductions in the frequency of these behaviours following surgery with analgesic treatment supported the hypothesis that they reflected post-operative pain. Ketoprofen and carprofen were equipotent and no dose related effects were apparent. Analgesic activity lasted between 4 and 5 h with the 5 mg/kg dosage, this being estimated from the duration of overall and specific behaviour differences between saline and drug treated animals. The data provided substantial evidence as to the usefulness of behavioural criteria for estimating pain severity, and for the first time, the basis of a system for routine pain assessment and management in rats subjected to abdominal surgery.
SummaryBuprenorphine has been widely used for post-operative analgesia in laborat ory animals. Clinical ef®cacy has been dem onstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to post-operative pain. T his has resulted in recommendations of excessive dose rat es and inappropriate clinical indications. Studies involving tests of the ef®cacy of buprenorphine for alleviating behavioural or other signs of tonic (post-surgic al ) pain provide a more appropriat e estim at ion of the analgesic capabi lities of the drug. However, buprenorphine also has major effects upon the behaviour of normal (unoperated) animals, and this makes assessments of ef®cacy dif® cult with some of the systems used for scoring clinical pain. Nevertheless, our most recent studies of the effects of buprenorphine upon pain-related behaviours in rats support the view that it is an effective post-operative analgesic. T his short review critically reappraises the role of buprenorphine in this capacity and discusses a rational approach to the relief of pain in laboratory animals. We conclude that buprenorphine remains a valuable agent for pain relief in a wide range of animal species when used in an appropriate manner. Keywords Buprenorphine; pain; analgesia; animals; opioids; antinociception The analgesic effects of buprenorphineBuprenorphine has been extensively used as an analgesic both in laboratory and companion animals for almost two decades. It has recently been licensed for use in dogs and cats in the UK (`Vetergesic', Alstoe Veterinary, York, UK). T he potent analgesic effects of buprenorphine have been described in anim als presumed to be experiencing severe pain (Leese e t a l. 1988 ), and also varying degrees of post-surgical pain in clinical studies with rats, cats, dogs, pigs, sheep and also in man (Tabl e 1). T he antinociceptive properties of buprenorphine have also been determ ined, using numerous analgesiometric tests in a range of different species (see Table 2). An expanded account of availabl e data and more general conclusions concerning the ef®cacy of buprenorphine in some of these tests can be found in Table 3. Collectively, the results of the clinical and laboratory studies that have been undertaken provide compelling evidence that buprenorphine is not only a potent analgesic, but also that its durat ion of acti on is considerably longer than either morphine or pethidine (from between 6 and 12 h) although this
We have recently demonstrated dose-related analgesic-induced reductions in the occurrence of 7 behavioural activities following midline laparotomy in rats. For these behaviours to be useful in evaluating pain in laboratory rats they must be shown to occur after different types of surgery, and frequently enough to allow rapid scoring of animals. Here, the relevant behaviours were used to test the analgesic efficacy of meloxicam with a variation of our previous laparotomy model. As part of an unrelated project, 57 male Fischer rats were divided into groups to receive either saline (0.2 ml/100g s.c.), meloxicam (0.5, 1 or 2 mg/kg s.c.) or carprofen (2.5, 5, or 10 mg/kg s.c.) 1h before surgery. Behaviour data were collected for 10 min following 25 min of recovery from isoflurane anaesthesia. The cumulative frequencies of back arching, fall/stagger, writhe and poor gait were used to compute a composite behaviour score. Irrespective of whether analyses included only 5 or all 10 min of the observation period, the relevant behaviours occurred significantly more often in rats given saline or low dose meloxicam than in those given 1 or 2 mg/kg of meloxicam, or any dose of carprofen. We conclude that this technique of quantifying post-surgery behaviour is an effective pain scoring method following abdominal surgery in rats, and that 1 mg/kg meloxicam significantly attenuates laparotomy induced pain. Since only a short observation period is required, this approach represents an important practical advance in assessing abdominal pain severity and clinical drug potency.
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