Hyperalgesia mediated by peripheral opiate receptors in the rat

Behavioural experiments were undertaken to investigate the possible functional significance of opiate receptors located at peripheral endings of primary sensory neurons. The responses of animals to noxious chemical stimuli applied to the ear (ear scratch test) were measured after local pretreatment of these areas with etorphine. Local etorphine administration produced a low dose hyperalgesia and high dose analgesia. Local as opposed to systemic effects of etorphine were inferred from the absence of effects on the contralateral vehicle-treated ear. Systemic administration of naloxone or of a quaternary opiate antagonist (MRZ 2663-BR), which is relatively ineffective in crossing the blood-brain barrier, blocked the low dose hyperalgesic effect of etorphine in the ear scratch test. As a test for the putative hyperalgesic function of peripheral sensory nerve opiate receptors, neonatal rats were treated with capsaicin (50 mg/kg s.c.) to destroy specifically the subpopulation of primary sensory neurons on which the peripheral opiate receptors are thought to be located, without markedly altering pain thresholds. As adults, these neonatally treated rats showed potentiated analgesic responses to systemic morphine, as would be predicted by central 'analgesic' opiate receptors now acting without opposition from peripheral 'hyperalgesic' opiate receptors. These findings suggest that opiate receptors on primary sensory neurons may mediate hyperalgesic functions and that endogenous opioids might normally play a role in the peripheral induction of irritation, inflammation and pain reactions.