The Role of Nociceptin/orphanin FQ in Pain Modulation

Nociceptin/orphanin FQ is a 17-amino-acid peptide, the sequence of which resembles those of opioid peptides (also see Chapter 72 and Chapter 73 ). Nociceptin/orphanin FQ precursor mRNA and peptide are present throughout descending pain control circuits. In the spinal cord, there is stronger nociceptin/orphanin FQ-receptor mRNA expression in the ventral horn than in the dorsal horn, but higher levels of ligand binding in the dorsal horn. Targeted disruption of the nociceptin/orphanin FQ receptor in mice had little effect on basal pain sensitivity in several measures, whereas targeted disruption of the N nociceptin/orphanin FQ precursor consistently elevated basal responses in the tail flick test, suggesting an important role for nociceptin/orphanin FQ in regulating basal pain sensitivity.^{[43] [44]} Intrathecal injections of nociceptin/orphanin FQ have been shown to be analgesic^[45] ; however, supraspinal administration has produced either hyperalgesia, antiopioid effects, or a biphasic hyperalgesic/analgesic response.^[46] It was shown that nociceptin/orphanin FQ inhibits both pain-facilitating and analgesia-facilitating neurons in the rostral ventromedial medulla.^[47] The effects of nociceptin/orphanin FQ on pain responses appear to depend on the preexisting state of pain in the animal. Yamamoto reported that intrathecal injection of nociceptin/orphanin FQ significantly attenuated the level of mechanical hyperalgesia induced by a skin incision, suggesting the involvement of the nociceptin/orphanin FQ receptor in maintaining postoperative pain.^[45] Physiologic implications of nociceptin/orphanin FQ remain to be elucidated.