Orphanin FQ/nociceptin: from neural circuitry to behavior.
Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the "orphan" opioid receptor ORL-1 (NOP(1)) was first identified in 1995. In the years since its discovery, a large body of evidence has accumulated showing that OFQ/N and its receptor are widely distributed in the nervous system, and showing that OFQ/N has potent and indiscriminate inhibitory actions on neurons in many regions. However, numerous studies investigating the functional role of OFQ/N in physiology or behavior have failed to provide a coherent view. Pain and analgesia have been the best studied, and administration of OFQ/N is reported to have no effect, to produce hyperalgesia, analgesia or anti-hyperalgesia. Effects of OFQ/N receptor antagonists have proved similarly contentious. In an attempt to resolve this controversy, we investigated the actions of OFQ/N on the activity of physiologically characterized neurons in the rostral ventromedial medulla, a region with a well-documented role in pain modulation(Heinricher et al., 1997). The results of those experiments demonstrate that this peptide is neither "anti-opioid" or "anti-hyperalgesic". It is simply inhibitory. For this reason, the effects seen in functional studies will only be fully understood when examined in the context of identified neural circuits.
Heinricher
Mary M
MM
Department of Neurological Surgery, Oregon Health and Science University, Portland 97239, USA. heinricm@ohsu.edu
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin