The role of 5-HT1A-receptors in fentanyl-induced bulbospinal inhibition ofa spinal withdrawal reflex in the rabbit

The sural to gastrocnemius withdrawal reflex is inhibited after injection o f the OP3 (mu)-receptor-selective opioid fentanyl into the fourth ventricle of decerebrated rabbits. This effect is abolished by complete section of t he spinal cord but not by the selective alpha(2)-adrenoceptor antagonist RX 821002 (Clarke RW, Parry-Baggott C, Houghton AK, Ogilvie J. The involvemen t of bulbo-spinal pathways in fentanyl-induced inhibition of spinal withdra wal reflexes in the decerebrated rabbit. Pain 1998;78;197-207). We have now investigated the role of 5HT(1A) receptors in mediating the descending inh ibition activated by intraventricular fentanyl. In the control state, intra ventricular fentanyl (330 mu g/kg) inhibited gastrocnemius reflex responses to a median of 34% of pre-drug levels. After intrathecal administration of the selective 5-HT1A receptor antagonist WAY-100635 (100 mu g), fentanyl r educed reflex responses to 83% of pre-fentanyl values, significantly less i nhibition than in the control state. In a separate group of experiments, in travenous fentanyl (0.3-30 mu g/kg) depressed the sural-gastrocnemius refle x to 17% of pre-drug controls. This inhibition was not affected by intrathe cal WAY-100635 (100 mu g), but combined administration of the 5-HT1A antago nist with RX 821002 (100 mu g) significantly reduced the effectiveness of i .v. fentanyl. After the highest dose reflexes were 37% of pre-fentanyl leve ls. These data show that the bulbospinal inhibition activated by fentanyl i s mediated, at least in part, by activation of spinal 5-HT1A receptors. Tha t blockade of these receptors failed to influence the inhibition induced by i.v. fentanyl might be taken to mean that the brain-stem action of fentany l does not contribute significantly to the systemic actions of this opioid. A more probable explanation is that, in the preparation used in the presen t study, the bulbospinal and direct spinal actions of fentanyl occlude each other to produce an overall inhibition that is less than the sum of the tw o effects. (C) 2000 International Association for the Study of Pain. Publis hed by Elsevier Science B.V. All rights reserved.