A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin.
Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing mu opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.
Pan
Z
Z
Department of Neurology, The W.M. Keck Center for Integrative Neuroscience, University of California, San Francisco 94143, USA. zzp@itsa.ucsf.edu
Hirakawa
N
N
Fields
H L
HL
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016764:Cell Polarity; D004553:Electric Conductivity; D006930:Hyperalgesia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D000097629:Nociceptin
D018847:Opioid Peptides; D011188:Potassium; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000097629:Nociceptin