SEMINAR: REPERFUSION HYPERALGESIA: FROM RAT TAIL TO DYSMENORRHOEA

If a tourniquet is applied to the base of a rat’s tail and then released, the tail becomes hypersensitive to subsequent noxious challenges. A similar phenomenon may underlie dysmenorrhoeic pain. Reperfusion hyperalgesia has characteristics similar to those of inflammatory and post-traumatic hyperalgesia, which are also of substantial clinical importance. We have measured the responses of neurones with receptive fields in the tail, in the thalamus, spinal cord and coccygeal nerve of rats, and identified neurones with responses to noxious challenge during reperfusion which are congruent with the behavioural responses of the rats. We also have established that the behavioural hyperalgesia can be blocked with opiates, cyclo-oxygenase inhibitors, NMDA receptor antagonists, benzodiazepines and histamine antagonists; for some of these pharmacological agents we have investigated how the underlying neuronal pathways respond, and again the neuronal and behavioural responses are congruent. Apart from revealing the neurophysiological and neurochemical substrates of an important clinical phenomenon, our investigations have allowed us to develop an assay for new pain-relieving drugs, with important scientific and ethical advantages over other animal-based assays.