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

Reference

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

Abstract

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