Nociceptin/orphanin FQ in spinal nociceptive mechanisms under normal and pathological conditions

Nociceptin and its receptor are present in dorsal spinal cord, indicating a possible role for this peptide in pain transmission. The majority of funct ional studies using behavioral and electrophysiological studies have shown that nociceptin applied at spinal level produces antinociception through pr e- and post-synaptic mechanisms. The spinal inhibitory effect of nociceptin is not sensitive to antagonists of opioid receptors such as naloxone. Thus , nociceptin-induced antinociception is mediated by a novel mechanism indep endent of activation of classic opioid receptors. This has raised the possi bility that agonists of the nociceptin receptor may represent a novel class of analgesics. Supporting this hypothesis, several groups have shown that intrathecal nociceptin alleviated hyperalgesic and allodynic responses in r ats after inflammation or partial peripheral nerve injury. Electrophysiolog ical studies have also indicated that the antinociceptive potency of spinal nociceptin is maintained or enhanced after nerve injury. It is concluded t hat the predominant action of nociceptin in the spinal cord appears to be i nhibitory. The physiological role of nociceptin in spinal nociceptive mecha nisms remains to be defined. Moreover, further evaluation of nociceptin as a new analgesic calls the development of non-peptide brain penetrating agen ts. (C) 2000 Elsevier Science Inc. All rights reserved.