Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling

Jennie L. Conroy, Cheng Fang, Jun Gu, Scott O. Zeitlin, Weizhu Yang, Jun Yang, Melissa A. Vanalstine, Julia W. Nalwalk, Phillip J. Albrecht, Joseph E. Mazurkiewicz, Abigail Snyder-Keller, Zhixing Shan, Shao Zhong Zhang, Mark P. Wentland, Melissa Behr, Brian I. Knapp, Jean M. Bidlack, Obbe P. Zuiderveld, Rob Leurs, Xinxin DingLindsay B. Hough

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

To assess the importance of brain cytochrome P450 (P450) activity in 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.

Original languageEnglish (US)
Pages (from-to)284-286
Number of pages3
JournalNature neuroscience
Volume13
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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