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 Ding; Lindsay B. Hough

doi:10.1038/nn.2497

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 Ding

Lindsay B. Hough

Research output: Contribution to journal › Article › peer-review

50 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 language	English (US)
Pages (from-to)	284-286
Number of pages	3
Journal	Nature neuroscience
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/nn.2497
State	Published - Mar 2010
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1038/nn.2497

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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

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

@article{bd621002888742ccbf65a0f93a163ab1,

title = "Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling",

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.",

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

note = "Funding Information: The authors gratefully acknowledge the use of the Molecular Genetics and the Biochemistry Cores of the Wadsworth Center. We thank A. Verschoor for reading the manuscript, Y. Weng for assistance with chemical analysis, J. Phillips (Curragh Chemistries) for CC12 and A. Mongin for valuable discussions. This work was supported in part by US National Institutes of Health grants ES07462 (X.D.), DA03816 (L.B.H.), DA00360 (J.M.B.) and NS43466 (S.O.Z.).",

year = "2010",

month = mar,

doi = "10.1038/nn.2497",

language = "English (US)",

volume = "13",

pages = "284--286",

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AU - Conroy, Jennie L.

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AU - Gu, Jun

AU - Zeitlin, Scott O.

AU - Yang, Weizhu

AU - Yang, Jun

AU - Vanalstine, Melissa A.

AU - Nalwalk, Julia W.

AU - Albrecht, Phillip J.

AU - Mazurkiewicz, Joseph E.

AU - Snyder-Keller, Abigail

AU - Shan, Zhixing

AU - Zhang, Shao Zhong

AU - Wentland, Mark P.

AU - Behr, Melissa

AU - Knapp, Brian I.

AU - Bidlack, Jean M.

AU - Zuiderveld, Obbe P.

AU - Leurs, Rob

AU - Ding, Xinxin

AU - Hough, Lindsay B.

N1 - Funding Information: The authors gratefully acknowledge the use of the Molecular Genetics and the Biochemistry Cores of the Wadsworth Center. We thank A. Verschoor for reading the manuscript, Y. Weng for assistance with chemical analysis, J. Phillips (Curragh Chemistries) for CC12 and A. Mongin for valuable discussions. This work was supported in part by US National Institutes of Health grants ES07462 (X.D.), DA03816 (L.B.H.), DA00360 (J.M.B.) and NS43466 (S.O.Z.).

PY - 2010/3

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AB - 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.

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ER -

Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling

Abstract

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