Progesterone and allopregnanolone rapidly attenuate estrogen-associated mechanical allodynia in rats with persistent temporomandibular joint inflammation

dc.contributor.authorHornung, Rebecca S.
dc.contributor.authorBenton, William L.
dc.contributor.authorTongkhuya, Sirima
dc.contributor.authorUphouse, Lynda
dc.contributor.authorKramer, Phillip R.
dc.contributor.authorAveritt, Dayna L.
dc.descriptionArticle originally published in Frontiers in Integrative Neuroscience, 14. English. Published online May 2020.
dc.description.abstractTemporomandibular joint disorder (TMD) is associated with pain in the joint (temporomandibular joint, TMJ) and muscles involved in mastication. TMD pain dissipates following menopause but returns in some women undergoing estrogen replacement therapy. Progesterone has both anti-inflammatory and antinociceptive properties, while estrogen’s effects on nociception are variable and highly dependent on both natural hormone fluctuations and estrogen dosage during pharmacological treatments, with high doses increasing pain. Allopregnanolone, a progesterone metabolite and positive allosteric modulator of the GABAA receptor, also has antinociceptive properties. While progesterone and allopregnanolone are antinociceptive, their effect on estrogen-exacerbated TMD pain has not been determined. We hypothesized that removing the source of endogenous ovarian hormones would reduce inflammatory allodynia in the TMJ of rats and both progesterone and allopregnanolone would attenuate the estrogen-provoked return of allodynia. Baseline mechanical sensitivity was measured in female Sprague–Dawley rats (150–175 g) using the von Frey filament method followed by a unilateral injection of complete Freund’s adjuvant (CFA) into the TMJ. Mechanical allodynia was confirmed 24 h later; then rats were ovariectomized or received sham surgery. Two weeks later, allodynia was reassessed and rats received one of the following subcutaneous hormone treatments over 5 days: a daily pharmacological dose of estradiol benzoate (E2; 50 μg/kg), daily E2 and pharmacological to sub-physiological doses of progesterone (P4; 16 mg/kg, 16 μg/kg, or 16 ng/kg), E2 daily and interrupted P4 given every other day, daily P4, or daily vehicle control. A separate group of animals received allopregnanolone (0.16 mg/kg) instead of P4. Allodynia was reassessed 1 h following injections. Here, we report that CFA-evoked mechanical allodynia was attenuated following ovariectomy and daily high E2 treatment triggered the return of allodynia, which was rapidly attenuated when P4 was also administered either daily or every other day. Allopregnanolone treatment, whether daily or every other day, also attenuated estrogen-exacerbated allodynia within 1 h of treatment, but only on the first treatment day. These data indicate that when gonadal hormone levels have diminished, treatment with a lower dose of progesterone may be effective at rapidly reducing the estrogen-evoked recurrence of inflammatory mechanical allodynia in the TMJ.en_US
dc.identifier.citationThis is a published version of an article that is available at: Recommended citation: Hornung, R. S., Benton, W. L., Tongkhuya, S., Uphouse, L., Kramer, P. R., & Averitt, D. L. (2020). Progesterone and allopregnanolone rapidly attenuate estrogen-associated mechanical allodynia in rats with persistent temporomandibular joint inflammation. Frontiers in Integrative Neuroscience, 14. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.publisherFrontiers Mediaen_US
dc.rights.licenseCC BY 4.0
dc.rights.license© 2020 Hornung, Benton, Tongkhuya, Uphouse, Kramer and Averitt
dc.subjectOrofacial painen_US
dc.subjectMechanical allodyniaen_US
dc.subjectTemporomandibular jointen_US
dc.subjectInflammatory painen_US
dc.subjectGonadal hormonesen_US
dc.titleProgesterone and allopregnanolone rapidly attenuate estrogen-associated mechanical allodynia in rats with persistent temporomandibular joint inflammationen_US


Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Averitt-Progesterone and Allopregnanolone.pdf
2.34 MB
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
1.68 KB
Item-specific license agreed upon to submission