Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling

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

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Veröffentlicht in:	Nature neuroscience 2010-03, Vol.13 (3), p.284-286
Hauptverfasser:	Ding, Xinxin, Hough, Lindsay B, 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
Format:	Artikel
Sprache:	eng
Schlagworte:	631/250/516 631/378/1697 692/700/565/411 Analgesics Analgesics, Opioid - administration & dosage Analgesics, Opioid - pharmacology Animal Genetics and Genomics Animals Antibodies Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Brain Brain - drug effects Brain - enzymology Brain - metabolism brief-communication Cytochrome Cytochrome P-450 Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System - drug effects Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Dose-Response Relationship, Drug Drug dosages Enzyme Inhibitors - pharmacology Female GABA Genotype & phenotype Male Measurement Mice Mice, Transgenic Morphine Morphine - administration & dosage Morphine - pharmacology Narcotics Neural Pathways - drug effects Neural Pathways - enzymology Neural Pathways - metabolism Neurobiology Neurons - drug effects Neurons - enzymology Neurons - metabolism Neurosciences Pain - drug therapy Pain - enzymology Pain - metabolism Physiological aspects Rats Rats, Sprague-Dawley Receptors, Opioid, mu - metabolism Signal Transduction Time Factors
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Zusammenfassung:	To assess the importance of brain cytochrome P450 (P450) activity in μ 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.
ISSN:	1097-6256 1546-1726
DOI:	10.1038/nn.2497