Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling
JL Conroy, C Fang, J Gu, SO Zeitlin, W Yang… - Nature …, 2010 - nature.com
Nature neuroscience, 2010•nature.com
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.
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.
Abstract
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.
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