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 Citations (Scopus)

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 1 2010
Externally publishedYes

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Drug Dose Response Relationship
Neural Pathways
mu Opioid Receptor
Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Morphine
Opioid Analgesics
Transgenic Mice
Sprague Dawley Rats
Analgesics
Signal Transduction
Neurons
Pain
Brain
Pharmacology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Conroy, J. L., Fang, C., Gu, J., Zeitlin, S. O., Yang, W., Yang, J., ... 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

Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. / 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.

In: Nature neuroscience, Vol. 13, No. 3, 01.03.2010, p. 284-286.

Research output: Contribution to journalArticle

Conroy, JL, Fang, C, Gu, J, Zeitlin, SO, Yang, W, Yang, J, Vanalstine, MA, Nalwalk, JW, Albrecht, PJ, Mazurkiewicz, JE, Snyder-Keller, A, Shan, Z, Zhang, SZ, Wentland, MP, Behr, M, Knapp, BI, Bidlack, JM, Zuiderveld, OP, Leurs, R, Ding, X & Hough, LB 2010, 'Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling', Nature neuroscience, vol. 13, no. 3, pp. 284-286. https://doi.org/10.1038/nn.2497
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. / Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. In: Nature neuroscience. 2010 ; Vol. 13, No. 3. pp. 284-286.
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