Nociceptin/orphanin FQ: pain, stress and neural circuits.
First isolated some 10 years ago as the endogenous ligand for the "orphan opioid receptor" (ORL-1, now designated NOP), nociceptin/orphanin FQ (N/OFQ) has proved to be a potent inhibitory neuropeptide found across the neuraxis. Because of the homologies between opioids and N/OFQ, functional studies of this peptide have focused most heavily on pain and analgesia. This behavioral literature has been marked by a lack of consistency across laboratories, but much of the data can be explained by considering the potent inhibitory actions of N/OFQ in well-defined modulatory circuits. Presently, the most closely studied such circuit is the rostral ventromedial medulla (RVM), where administration of N/OFQ can block opioid analgesia (by inhibiting opioid-activated pain-inhibiting neurons), but under other conditions produces apparent hypoalgesia (by inhibiting pain-facilitating neurons). The net behavioral effect of N/OFQ in the RVM thus depends on whether experimental conditions are such that the pain-facilitating or pain-inhibiting neurons are active at the time the peptide is given. An important recent finding is that N/OFQ antagonists have antinociceptive properties when given supra-spinally. Although the likelihood of interactions between stress and analgesia systems must be considered in interpreting these data, they suggest that N/OFQ antagonists have potential as clinically useful analgesic drugs.
Department of Neurological Surgery, L-472, Oregon Health and Science University, Portland, OR 97239, USA. heinricm@ohsu.edu
Mary M
MM
Heinricher
D000818:Animals; D001519:Behavior / Q000187:drug effects / Q000502:physiology; D008024:Ligands; D009292:Narcotic Antagonists; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D008024:Ligands; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin