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Bidirectional modulatory effect of orphanin FQ on morphine-induced analgesia: antagonism in brain and potentiation in spinal cord of the rat
Authors:Jin-Hua Tian  Wei Xu  Yuan Fang  Jeffrey S Mogil  Judith E Grisel  David K Grandy  Ji-Sheng Han
Institution:Neuroscience Research Center, Beijing Medical University, Beijing, China;*Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland, OR 97201;Vollum Institute for Advanced Biomedical Sciences, Oregon Health Sciences University, Portland, OR 97201, U.S.A.
Abstract:
  1. The present study was designed to investigate further the effects of the newly discovered orphanin FQ (OFQ)–the endogenous ligand for the orphan opioid receptor (called, e.g., ORL1 and LC132)–on pain modulation in the rat. We used the tail-flick assay as a nociceptive index.
  2. When injected into a cerebral ventricle, OFQ (4 fmol–10 nmol) has no effect on basal tail-flick latency by itself at any dose, but dose-dependently antagonizes systemic morphine analgesia (400 fmol–50 nmol).
  3. Injected intrathecally, OFQ (3 and 10 nmol) displayed an analgesic effect without producing motor dysfunction, and potentiated morphine analgesia (1 and 10 nmol).
  4. The anti-opioid effect of OFQ in rat brain and the high level of expression of LC132/ORL1 receptor in the locus coeruleus indicated a possible role of OFQ in the precipitation of opiate withdrawal symptoms. However, no such precipitation was observed by OFQ in morphine-dependent rats.
Keywords:Analgesia  anti-opioid  ORL1/LC132  orphanin FQ/nociceptin  morphine withdrawal
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