Infusion of Gabr6 siRNA into the trigeminal ganglia increased the myogenic orofacial nociceptive response of ovariectomized rats treated with 17-estradiol.
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abstract
High levels of 17-estradiol (E2) have been found to reduce inflammatory temporomandibular joint (TMJ) pain. A search for genes effected by a high concentration of estradiol showed an increase in GABAA receptor subunit alpha 6 (Gabr6) in the trigeminal ganglia (TG). Blockade of Gabr6 expression in the TG increases masseter muscle nociception in male rats, but the relationship between estradiol's effect on nociception and Gabr6 expression remains unclear in females. To address this knowledge gap we hypothesized that reducing Gabr6 expression in the TG will increase the orofacial nociceptive response of ovariectomized female rats treated with estradiol. To administer hormone osmotic pumps were placed in rats that dispensed a low diestrus plasma concentration of 17-estradiol, in addition, 17-estradiol was injected to produce a high proestrus plasma concentration of estradiol. A ligature was then placed around the masseter tendon to induce a nociceptive response; a model for TMJ muscle pain. Gabr6 small interfering RNA (siRNA) was later infused into the TG and the nociceptive response was measured using von Frey filaments and a meal duration assay. GABAA receptor expression was measured in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1). Ligature significantly increased the nociceptive response but a high proestrus concentration of 17-estradiol attenuated this response. Gabr6 siRNA infusion decreased Gabr6 expression in the TG and Vc-C1 but increased the nociceptive response after 17-estradiol treatment. The results suggest estradiol decreased the orofacial nociceptive response, in part, by causing an increase in Gabr6 expression.
