Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone

dc.contributor.authorHornung, Rebecca S.
dc.contributor.authorRaut, Namrata G.R.
dc.contributor.authorCantu, Daisy J.
dc.contributor.authorLockhart, Lauren M.
dc.contributor.authorAveritt, Dayna L.
dc.creator.orcidhttps://orcid.org/0000-0001-8345-4988
dc.date.accessioned2023-02-27T15:32:26Z
dc.date.available2023-02-27T15:32:26Z
dc.date.issued2022
dc.descriptionArticle originally published by Molecular Pain, 18, 174480692110692. English. Published online 2022. https://doi.org/10.1177/17448069211069255.
dc.descriptionThis research was funded in part by National Institutes of Health NIDCR grant DE025970 awarded to DLA and in part by a TWU Experiential Student Program Grant and Center for Student Research Small Grant awarded to RSH.
dc.description.abstractOrofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone’s activity in the trigeminal system. Progesterone has been reported to exert protective effects through actions at intracellular progesterone receptors (iPR), membrane-progesterone receptors (mPR), or sigma 1 receptors (Sig-1R). Of these, the iPR and Sig-1R have been reported to have a role in pain. Progesterone can also have antinociceptive effects through its metabolite, allopregnanolone. Two enzymes, 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD), are required for the metabolism of progesterone to allopregnanolone. Both progesterone and allopregnanolone rapidly attenuate pain sensitivity, implicating action of either progesterone at Sig-1R and/or conversion to allopregnanolone which targets GABAA receptors. In the present study, we investigated whether Sig-1 Rs are expressed in nociceptors within the trigeminal ganglia of cycling female rats and whether the two enzymes required for progesterone metabolism to allopregnanolone, 5α-reductase and 3α-hydroxysteroid dehydrogenase, are also present. Adult female rats from each stage of the estrous cycle were rapidly decapitated and the trigeminal ganglia collected. Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.en_US
dc.identifier.citationThis is the published version of an article that is available at https://doi.org/10.1177/17448069211069255. Recommended citation: Hornung, R. S., Raut, N. G. R., Cantu, D. J., Lockhart, L. M., & Averitt, D. L. (2022). Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone. Molecular Pain, 18, 174480692110692. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.identifier.urihttps://hdl.handle.net/11274/14519
dc.identifier.urihttps://doi.org/10.1177/17448069211069255
dc.language.isoen_USen_US
dc.publisherSAGE Publicationsen_US
dc.rights.holder© The Author(s) 2022.
dc.rights.licenseCC BY-NC
dc.subjectProgesteroneen_US
dc.subjectTrigeminal sensory neuronsen_US
dc.subjectAllopregnanoloneen_US
dc.subjectSigma-1 receptoren_US
dc.subject5α-reductaseen_US
dc.subject3α-hydroxysteroid dehydrogenaseen_US
dc.titleSigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesteroneen_US
dc.typeArticleen_US

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