Sex differences in μ-opioid receptor expression in the rat midbrain periaqueductal gray are essential for eliciting sex differences in morphine analgesia

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dc.contributor.authorLoyd, Dayna R.
dc.contributor.authorWang, Xioaya
dc.contributor.authorMurphy, Anne Z.
dc.creator.orcidhttps://orcid.org/0000-0001-8345-4988
dc.date.accessioned2019-10-02T18:22:34Z
dc.date.available2019-10-02T18:22:34Z
dc.date.issued2008
dc.description.abstractOpioid-based narcotics are the most widely prescribed therapeutic agent for the alleviation of persistent pain; however, it is becoming increasingly clear that morphine is significantly less potent in women compared with men. Morphine primarily binds to μ-opioid receptors (MORs), and the periaqueductal gray (PAG) contains a dense population of MOR-expressing neurons. Via its descending projections to the rostral ventromedial medulla and the dorsal horn of the spinal cord, the PAG is considered an essential neural substrate for opioid-based analgesia. We hypothesized that MOR expression in the PAG was sexually dimorphic, and that these sex differences contribute to the observed sex differences in morphine potency. Using immunohistochemistry, we report that males had a significantly higher expression of MOR in the ventrolateral PAG compared with cycling females, whereas the lowest level of expression was observed in proestrus females. CFA-induced inflammatory pain produced thermal hyperalgesia in both males and females that was significantly reversed in males with a microinjection of morphine into the ventrolateral PAG; this effect was significantly greater than that observed in proestrus and estrus females. Selective lesions of MOR-expressing neurons in the ventrolateral PAG resulted in a significant reduction in the effects of systemic morphine in males only, and this reduction was positively correlated with the level of MOR expression in the ventrolateral PAG. Together, these results provide a mechanism for sex differences in morphine potency.en_US
dc.identifier.citationThis is a published version of an article that is available at: https://doi.org/10.1523/JNEUROSCI.4123-08.2008. Recommended citation: Loyd, D. R., Wang, X., & Murphy, A. Z. (2008). Sex differences in μ-opioid receptor expression in the rat midbrain periaqueductal gray are essential for eliciting sex differences in morphine analgesia. Journal of Neuroscience, 28(52), 14007–14017. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.identifier.urihttps://doi.org/10.1523/JNEUROSCI.4123-08.2008
dc.identifier.urihttps://hdl.handle.net/11274/11850
dc.language.isoen_USen_US
dc.publisherSociety for Neuroscienceen_US
dc.rights.holderCopyright 2008 Society for Neuroscience
dc.subjectDermorphin-saporinen_US
dc.subjectIntra-vlPAGen_US
dc.subjectEstrous cycleen_US
dc.subjectPainen_US
dc.subjectInflammationen_US
dc.subjectOpiateen_US
dc.titleSex differences in μ-opioid receptor expression in the rat midbrain periaqueductal gray are essential for eliciting sex differences in morphine analgesiaen_US
dc.typeArticleen_US

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