A pharmacological overview of opioid mechanisms mediating analgesia and hyperalgesia.

We present a review of the opioid mechanism of analgesia and hyperalgesia and attempt to integrate some of the most recent findings in neuro-anatomy, neuro-physiology and neuropharmacology that indicate the presence of two distinct opioid systems; the one analgesic and the other hyperalgesic. The initial finding of a paradoxical effect of naloxone in which it was able to enhance the analgesic effects of nitrous oxide under certain circumstances led us to postulate the existence of such antagonistic opioid systems which appear to be important in the perception. The review details the further experimental evidence that has subsequently emerged to support our original hypothesis. This includes a hypothesis developed by other workers (viz. diffuse noxious inhibitory control system) which has attempted to explain the analgesic effects of naloxone. Recent anatomical evidence locating the hyperalgesic system in the medullary pontine region is given.