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

J.L. Conroy; C. Fang; J. Gu; S.O. Zeitlin; W Yang; M.A. VanAlstine; J.W. Nalwalk; P.J. Albrecht; J.E. Mazurkiewicz; A. Snyder-Keller; Z. Shan; S.Z. Zhang; M.P. Wentland; ~M. Behr; B.I. Knapp; J.M. Bidlack; O.P. Zuiderveld; R. Leurs; X. Ding; L.B> Hough

doi:10.1038/nn.2497

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

J.L. Conroy, C. Fang, J. Gu, S.O. Zeitlin, W Yang, M.A. VanAlstine, J.W. Nalwalk, P.J. Albrecht, J.E. Mazurkiewicz, A. Snyder-Keller, Z. Shan, S.Z. Zhang, M.P. Wentland, ~M. Behr, B.I. Knapp, J.M. Bidlack, O.P. Zuiderveld, R. Leurs, X. Ding, L.B> Hough

Research output: Contribution to Journal › Article › Academic › peer-review

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. © 2010 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	284-286
Journal	Nature Neuroscience
Volume	13
DOIs	https://doi.org/10.1038/nn.2497
Publication status	Published - 2010

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Conroy, J. L., Fang, C., Gu, J., Zeitlin, S. O., Yang, W., 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., Ding, X., & Hough, L. B. (2010). Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. Nature Neuroscience, 13, 284-286. https://doi.org/10.1038/nn.2497

@article{1542979206f34f80ba91c8728d6ef8ff,

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. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",

author = "J.L. Conroy and C. Fang and J. Gu and S.O. Zeitlin and W Yang and M.A. VanAlstine and J.W. Nalwalk and P.J. Albrecht and J.E. Mazurkiewicz and A. Snyder-Keller and Z. Shan and S.Z. Zhang and M.P. Wentland and ~M. Behr and B.I. Knapp and J.M. Bidlack and O.P. Zuiderveld and R. Leurs and X. Ding and L.B> Hough",

year = "2010",

doi = "10.1038/nn.2497",

language = "English",

volume = "13",

pages = "284--286",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

}

Conroy, JL, Fang, C, Gu, J, Zeitlin, SO, Yang, W, 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, pp. 284-286. https://doi.org/10.1038/nn.2497

TY - JOUR

T1 - Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling.

AU - Conroy, J.L.

AU - Fang, C.

AU - Gu, J.

AU - Zeitlin, S.O.

AU - Yang, W

AU - VanAlstine, M.A.

AU - Nalwalk, J.W.

AU - Albrecht, P.J.

AU - Mazurkiewicz, J.E.

AU - Snyder-Keller, A.

AU - Shan, Z.

AU - Zhang, S.Z.

AU - Wentland, M.P.

AU - Behr, ~M.

AU - Knapp, B.I.

AU - Bidlack, J.M.

AU - Zuiderveld, O.P.

AU - Leurs, R.

AU - Ding, X.

AU - Hough, L.B>

PY - 2010

Y1 - 2010

N2 - 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. © 2010 Nature America, Inc. All rights reserved.

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. © 2010 Nature America, Inc. All rights reserved.

U2 - 10.1038/nn.2497

DO - 10.1038/nn.2497

M3 - Article

SN - 1097-6256

VL - 13

SP - 284

EP - 286

JO - Nature Neuroscience

JF - Nature Neuroscience

ER -

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

Abstract

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