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.