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Molecular Pain

, 9:45

First Online: 08 September 2013Received: 04 June 2013Accepted: 03 September 2013


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

KeywordsSex differences Opioid analgesia Opioid addiction Opioid receptors Estrogen receptors AbbreviationsACAdenylate cyclase

DORδ-opioid receptor


ERαEstrogen receptor α

ERβEstrogen receptor β

GPR30-GPEREstrogen G protein-coupled receptor

KORκ-opioid receptor

MAPKMitogen-activated protein kinases

MORμ-opioid receptor

NOPNociceptin-orphanin FQ peptide

ORL1Opioid receptor-like 1 receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-9-45 contains supplementary material, which is available to authorized users.

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Autor: Cynthia Wei-Sheng Lee - Ing-Kang Ho



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