Options for management of acute pain in the rat

Clinical recommendations for analgesics in laboratory rodents are usually derived from basic research. However, animal models of pain often involve withdrawal reflexes evoked by threshold-level stimuli, whereas pain associated with surgery or disease involves injury and inflammation. Moreover, the analgesics used in research tend to be chosen as exemplars of a drug class, without regard for whether the route of administration is practical, whether the drug has useful kinetics or whether the side effects are tolerable. This paper provides data on the efficacy of drugs from four classes, using the formalin test as a model of injury-induced pain. Formalin (50 microliters, 2.5 per cent) was injected subcutaneously into a rat's paw and the behavioural response (lifting or licking of the paw) was recorded. Buprenorphine at 0.1 mg/kg and dipyrone at 200 mg/kg completely suppressed the pain responses. When formalin was injected six hours after buprenorphine or dipyrone, pain scores were 30 per cent of control scores. In the absence of pain and handling, 0.6 mg/kg buprenorphine was lethal to 25 per cent of rats. Locomotor activity was slightly depressed by 300 mg/kg dipyrone. Xylazine at 2 mg/kg suppressed pain responses, but the analgesia had decreased to less than 50 per cent after two hours and the effects were variable thereafter; at 8 mg/kg rats were unresponsive to a strong pinch. Acepromazine at 2.5 mg/kg reduced pain to 20 per cent of control scores and this level of analgesia was maintained for six hours; neuroleptic effects were prominent at 5 mg/kg.