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- Title
Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling.
- Authors
Conroy, Jennie L; Fang, Cheng; Gu, Jun; Zeitlin, Scott O; Yang, Weizhu; Yang, Jun; VanAlstine, Melissa A; Nalwalk, Julia W; Albrecht, Phillip J; Mazurkiewicz, Joseph E; Snyder-Keller, Abigail; Shan, Zhixing; Zhang, Shao-Zhong; Wentland, Mark P; Behr, Melissa; Knapp, Brian I; Bidlack, Jean M; Zuiderveld, Obbe P; Leurs, Rob; Ding, Xinxin; Hough, Lindsay B
- Abstract
To assess the importance of brain cytochrome P450 (P450) activity in mu opioid analgesic action, we generated a mutant mouse with brain neuron-specific reductions in P450 activity; these mice showed highly attenuated morphine antinociception compared with controls. Pharmacological inhibition of brain P450 arachidonate epoxygenases also blocked morphine antinociception in mice and rats. Our findings indicate that a neuronal P450 epoxygenase mediates the pain-relieving properties of morphine.
- Publication
Nature neuroscience, 2010, Vol 13, Issue 3, p284
- ISSN
1546-1726
- Publication type
Journal Article
- DOI
10.1038/nn.2497