The involvement of bulbospinal pathways in fentanyl-induced inhibition of spinal withdrawal reflexes in the decerebrated rabbit

The selective opioid OP3(mu)-receptor agonist fentanyl was administered via the intravenous, intrathecal and intraventricular routes to decerebrated r abbits in doses from 1-30 mu g/kg. Reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve were depressed by fentanyl given by all three routes. The opioid was most potent when given intrathecally and least potent when given into the fourth ventricle. Blocka de of spinal alpha(2)-adrenoceptors by intrathecal RX 821002 (100 mu g) red uced the effectiveness of intrathecal and low (< 3 mu g/kg) intravenous dos es of fentanyl, but did not affect or enhanced responses to high intraventr icular and intravenous doses. Spinalization reduced the effectiveness of in trathecal and intravenous fentanyl and abolished inhibition from intraventr icular dosing. These data show that fentanyl acts in the spinal cord and in the brain stem to suppress spinal reflexes, although very high doses were required for effects from the latter site. It appears that low intravenous doses of fentanyl act mainly in the spinal cord and that increasing the dos age recruits descending inhibition. The results of alpha(2)-adrenocepror bl ockade indicate that the spinal inhibitory effects of opioids are enhanced by an interaction with endogenous noradrenaline in the spinal cord. Thus, t he full expression of the spinal inhibitory effects of fentanyl is dependen t on brain stem cell groups, either as a source of noradrenaline input to t he spinal cord, or as a site from which opioids can activate descending inh ibitory systems. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.