Unaltered peripheral excitatory actions of nociceptin contrast with enhanced spinal inhibitory effects after carrageenan inflammation: an electrophysiological study in the rat

Abstract

Nociceptin (orphanin FQ) is the endogenous agonist of the opioid receptor-like (ORL-1) receptor. The actions of this peptide have been studied extensively at a number of sites with diverse actions being reported. Here, in a rat model of peripheral inflammation, we examine the effects of nociceptin on the responses of dorsal horn neurones when applied directly to the spinal cord and, in separate studies, into the peripheral receptive fields in the hindpaw of the halothane anaesthetized rat. As changes in the receptor density and expression of the message for nociceptin have been reported after inflammation we have compared these actions to previously reported effects in normal animals. The dose-dependent inhibitory actions of nociceptin on C-fibre evoked responses and input (measures of presumed pre-synaptic excitability) are increased 3-4 h after inflammation whereas its inhibitory effects on post-synaptic mechanisms (wind-up) remain unchanged. These inhibitory effects were partly reversible by high doses of naloxone. This increased potency of nociceptin after inflammation is consistent with an increased receptor density in the superficial spinal cord. In contrast, the peripheral administration of nociceptin produced dose-dependent excitations of dorsal horn neurones and a degree of sensitization to mechanical stimuli. This peripheral action was unchanged after inflammation. These diverse site-dependent actions of nociceptin further emphasize the complexities of this novel opioid system.