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.