Background. Women with temporomandibular disorders (TMDs) experience some amelioration of pain during pregnancy. Progesterone increases dramatically and steadily during pregnancy. Sodium channel 1.7 (Nav1.7) plays a prominent role in pain perceptions, as evidenced by deletion of Nav1.7 alone leading to a complete loss of pain. In a previous study, we showed that Nav1.7 in trigeminal ganglion (TG) is involved in allodynia of inflamed temporomandibular joint (TMJ). Whether progesterone modulates allodynia of inflamed TMJ through Nav1.7 in TG remains to be investigated. Methods. The effects of progesterone on sodium currents of freshly isolated TG neurons were examined using whole-cell recording. Female rats were ovariectomized and treated with increasing doses of progesterone for 10 days. Complete Freund’s adjuvant was administered intra-articularly to induce TMJ inflammation. TMJ nociceptive responses were evaluated by head withdrawal thresholds. Real-time PCR and Western blotting were used to examine Nav1.7 mRNA and protein expression in TG. Immunohistofluorescence was used to examine the colocalization of progesterone receptors (PRα/β) and Nav1.7 in TG. Results. Whole-cell recording showed that progesterone could attenuate sodium currents. Moreover, progesterone dose-dependently downregulated Nav1.7 mRNA expression and reduced the sensitivity of TMJ nociception in ovariectomized rats. Furthermore, treatment with progesterone attenuated allodynia of inflamed TMJ in a dose-dependent manner and repressed inflammation-induced Nav1.7 mRNA and protein expression in ovariectomized rats. The progesterone receptor antagonist, RU-486, partially reversed the effect of progesterone on allodynia of inflamed TMJ and TMJ inflammation-induced Nav1.7 mRNA and protein expression. Conclusion. Progesterone, by modulating trigeminal ganglionic Nav1.7, may represent a promising agent to prevent allodynia of inflamed TMJ.

中文翻译：

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孕酮通过调节三叉神经节中的电压门控钠通道1.7减轻发炎的颞下颌关节的异常性疼痛。

背景。患有颞下颌关节疾病（TMD）的妇女在怀孕期间会缓解疼痛。孕期黄体酮急剧稳定地增加。钠通道1.7（Nav1.7）在疼痛感觉中起着重要作用，这可以通过仅删除Nav1.7导致疼痛完全消失来证明。在先前的研究中，我们显示三叉神经节（TG）中的Nav1.7与发炎的颞下颌关节（TMJ）的异常性疼痛有关。孕激素是否通过Nav1.7调节TG中发炎的TMJ的异常性疼痛仍有待研究。方法。使用全细胞记录检查了孕酮对新鲜分离的TG神经元钠电流的影响。雌性大鼠被切除卵巢并用增加剂量的孕激素治疗10天。关节内施用完全弗氏佐剂以诱导TMJ炎症。通过头部退缩阈值评估TMJ伤害感受反应。实时荧光定量PCR和蛋白质印迹用于检查TG中的Nav1.7 mRNA和蛋白表达。免疫组织荧光法检测孕激素受体的共定位（PR α / β）和Nav1.7在TG。结果。全细胞记录表明，孕酮可以减弱钠电流。此外，黄体酮剂量依赖性下调去卵巢大鼠中Nav1.7 mRNA的表达并降低TMJ伤害感受的敏感性。此外，黄体酮治疗以剂量依赖的方式减轻了发炎的TMJ的异常性疼痛，并抑制了卵巢切除大鼠的炎症诱导的Nav1.7 mRNA和蛋白表达。孕酮受体拮抗剂RU-486可以部分逆转孕酮对发炎的TMJ和TMJ炎症诱导的Nav1.7 mRNA和蛋白表达的异常性疼痛的作用。结论。孕激素通过调节三叉神经节Nav1.7，可能代表一种有希望的预防炎症性TMJ异常性疼痛的药物。