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 journalArticle

44 Scopus citations


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
Issue number3
StatePublished - Mar 1 2010
Externally publishedYes


ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Conroy, J. L., Fang, C., Gu, J., Zeitlin, S. O., Yang, W., Yang, J., Vanalstine, M. A., Nalwalk, J. W., Albrecht, P. J., Mazurkiewicz, J. E., Snyder-Keller, A., Shan, Z., Zhang, S. Z., Wentland, M. P., Behr, M., Knapp, B. I., Bidlack, J. M., Zuiderveld, O. P., Leurs, R., ... Hough, L. B. (2010). Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. Nature neuroscience, 13(3), 284-286. https://doi.org/10.1038/nn.2497