Experimental pain and neuropeptides.

Noxious stimulus-induced changes in substance P (SP) release in the dorsal horn of the spinal cord and met-enkephalin release in the brain stem were investigated. For this purpose, a specially devised push-pull cannula system was used. Noxious stimuli were applied to the skin of the hind paw of rabbits and the lumbar dorsal horn was perfused using a push-pull cannula. Substance P concentration in the perfusate was assayed by radioimmunoassay. Noxious mechanical stimuli, but not thermal stimuli, increased the release of immunoreactive substance P (iSP). Innocuous stimuli did not affect the release of these peptides. Systemic administration of an analgesic dose of morphine (1 mg/kg) did not inhibit the iSP release induced by noxious stimuli. This suggests that morphine analgesia may not be mediated by a blocking action on SP release from the primary afferent terminals at the dorsal horn. The nucleus reticularis gigantocellularis (NRGC) of rat medulla oblongata was perfused in situ and the effects of noxious stimuli on the release of immunoreactive met-enkephalin were examined. Formalin and thermal stimuli, but not mechanical stimuli, increased the "tonic" release of immunoreactive met-enkephalin from NRGC. No "phasic" increase was observed following the three forms of stimulation. Topical application of dibucaine abolished the formalin-induced increase in the release of met-enkephalin. Therefore, the possibility that persistent noxious stimuli may activate the met-enkephalin-containing fibers in the NRGC must be given consideration.