Role of progesterone in sexual receptivity and orofacial pain

Two understudied disorders that are challenging to treat, sexual dysfunction and orofacial pain, are more prevalent in women and can be impacted by the gonadal hormone’s estrogen and progesterone. Estrogen’s effects on women’s health are well-known, but much less is known about progesterone. The data in this dissertation indicates progesterone may be beneficial in alleviating these two major issues in women. The major drug prescribed for depression increases brain serotonin levels resulting in sexual inhibition, which likely occurs via the serotonin 1A receptor (5-HT1A) as agonists inhibit sexual behavior. Interestingly, progesterone protects against sexual inhibition by an unknown mechanism that may involve the intracellular progesterone receptor (iPR). Here we hypothesized that progesterone’s attenuation of 5-HT1A receptor-induced sexual inhibition involves the iPR. Also, progesterone may be beneficial for alleviating temporomandibular joint disorder (TMD) pain, which is 3-4x more common in women. TMD pain dissipates during pregnancy and after menopause but reemerges for some post-menopausal women prescribed estrogen replacement therapy. Here we hypothesized that therapeutic doses of progesterone in female rats undergoing estrogen replacement would attenuate inflammatory pain behaviors of the temporomandibular joint (TMJ). Ovariectomized, estradiol-primed female rats injected with an iPR antagonist before or after progesterone, then injected with a 5-HT1A receptor agonist had sexual receptivity parameters measured to determine if progesterone’s attenuation of 5-HT1A receptor-induced sexual inhibition involves the iPR. To determine progesterone’s effect on TMD pain, female rats were tested for basal sensory thresholds at the TMJ then injected with complete Freund’s adjuvant (CFA) to trigger inflammation in the TMJ. Mechanical allodynia (developed touch sensitivity) was confirmed then rats were ovariectomized and reassessed for allodynia following various estrogen and progesterone treatment paradigms. This dissertation reports that progesterone acting at the iPR can attenuate 5-HT1A receptor-induced sexual inhibition (Chapter II), progesterone can rapidly attenuate estrogen-evoked TMD pain behaviors (Chapter III), and orofacial sensory neurons contain progesterone-metabolizing enzymes and receptors (Chapter IV). Overall, adjunctive progesterone treatment may provide beneficial gender-based therapies for women facing serotonin-induced sexual dysfunction or post-menopausal women experiencing a return in TMD pain following estrogen treatment.