Alpha 1-adrenoceptor-mediated sympathetically dependent mechanical hyperalgesia in the rat

The model of rolipram (a type IV phosphodiesterase inhibitor) induced prolongation (> 3 days) of the mechanical hyperalgesia produced by the intradermal injection of prostaglandin E2 in the hairy skin of the hindpaw of the rat, measured by the Randall-Selitto paw-withdrawal test, was employed to study mechanisms involved in the contribution of the sympathetic postganglionic neuron to mechanical hyperalgesia. Lumbar surgical sympathectomy prevented rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Decentralization of sympathetic postganglionic neurons innervating the hindpaw did not, however, effect rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Phentolamine, an alpha-adrenoceptor antagonist, and prazosin, an alpha 1-selective adrenoceptor antagonist, when given systemically or intradermally at the site of injection of prostaglandin E2 and rolipram, blocked rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Intrathecal administration of phentolamine and prazosin were, however, without effect on rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Yohimbine, an alpha 2-adrenoceptor antagonist given systemically, intradermally or intrathecally also did not produce any alteration in rolipram-induced prolongation of prostaglandin E2 hyperalgesia. We propose that sympathetic postganglionic neurons are involved in rolipram-induced prolongation of prostaglandin E2 hyperalgesia and that this form of sympathetically dependent hyperalgesia, which is independent of activity in preganglionic sympathetic neurons, is mediated by a peripheral alpha 1-adrenergic mechanism.