Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the\r\nopioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet,\r\nthe molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed\r\nthe literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant\r\nopioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also\r\nevaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and\r\nopioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and\r\nthe downstream gene transcriptional regulators.
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