孕激素通过调节三叉神经节中的电压门控钠离子通道 1.7 减轻炎性颞下颌关节的痛觉过敏。
Progesterone Attenuates Allodynia of Inflamed Temporomandibular Joint through Modulating Voltage-Gated Sodium Channel 1.7 in Trigeminal Ganglion.
机构信息
Third Clinical Division, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 10 Huayuan Lu, Haidian District, Beijing 100088, China.
Central Laboratory, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
出版信息
Pain Res Manag. 2020 Jul 25;2020:6582586. doi: 10.1155/2020/6582586. eCollection 2020.
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 (PR/) 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.
背景
患有颞下颌关节紊乱（TMD）的女性在怀孕期间会经历一些疼痛缓解。孕激素在怀孕期间会显著且稳定地增加。钠离子通道 1.7（Nav1.7）在疼痛感知中起着突出的作用，这一点可以通过单独缺失 Nav1.7 导致完全丧失疼痛来证明。在之前的一项研究中，我们发现三叉神经节（TG）中的 Nav1.7 参与了炎症性颞下颌关节（TMJ）的触诱发痛。孕激素是否通过 TG 中的 Nav1.7 调节炎症性 TMJ 的触诱发痛仍有待研究。
方法
使用全细胞膜片钳记录法检测孕激素对新鲜分离的 TG 神经元钠离子电流的影响。雌性大鼠被卵巢切除术，并接受递增剂量的孕激素治疗 10 天。向关节内注射完全弗氏佐剂以诱导 TMJ 炎症。通过头部退缩阈值评估 TMJ 伤害性反应。实时 PCR 和 Western blot 用于检测 TG 中 Nav1.7 mRNA 和蛋白表达。免疫荧光用于检测 TG 中孕激素受体（PR）和 Nav1.7 的共定位。
结果
全细胞膜片钳记录显示，孕激素可抑制钠离子电流。此外，孕激素呈剂量依赖性地下调 Nav1.7 mRNA 表达，并降低卵巢切除大鼠 TMJ 伤害感受的敏感性。此外，孕激素以剂量依赖性方式减轻炎症性 TMJ 的触诱发痛，并抑制卵巢切除大鼠 TMJ 炎症诱导的 Nav1.7 mRNA 和蛋白表达。孕激素受体拮抗剂 RU-486 部分逆转了孕激素对炎症性 TMJ 触诱发痛和 TMJ 炎症诱导的 Nav1.7 mRNA 和蛋白表达的影响。
结论
孕激素通过调节三叉神经节的 Nav1.7，可能成为预防炎症性 TMJ 触诱发痛的有前途的药物。
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