Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Center for Oral Functional Diagnosis, Treatment and Research, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Int J Mol Sci. 2021 Jun 28;22(13):6945. doi: 10.3390/ijms22136945.
Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.
颞下颌关节紊乱症（TMD）中的疼痛症状主要影响生育期女性，表明雌激素调节疼痛感知。然而，雌激素如何导致慢性 TMD 疼痛仍很大程度上不清楚。在本研究中，我们进行了行为测试、电生理学、Western blot 和免疫荧光实验，以研究雌激素在牙齿实验性咬合干扰（EOI）诱导的大鼠慢性咬肌机械性痛觉过敏中的作用及其潜在机制。我们发现，长期 17β-雌二醇（E2）替代以剂量依赖的方式加重去卵巢（OVX）大鼠 EOI 诱导的咬肌痛觉过敏。全细胞膜片钳记录表明，E2（100 nM）处理增强了分离的三叉神经节（TG）神经元的兴奋性，OVX 和 OVX EOI 大鼠中，EOI 增加了瞬时受体电位香草醛-1（TRPV1）的功能表达。此外，E2 替代上调了 EOI 处理的 OVX 大鼠中 TRPV1 的蛋白表达。重要的是，TG 内给予 TRPV1 拮抗剂 AMG-9810 强烈减弱了 E2 对 EOI 诱导的咬肌机械敏感性的易化作用。这些结果表明，E2 通过增加 TG 神经元兴奋性和 TRPV1 功能加重 EOI 诱导的慢性咬肌机械性痛觉过敏。我们的研究有助于阐明 E2 在慢性肌源性 TMD 疼痛中的作用，并为缓解雌激素敏感性疼痛提供新的治疗靶点。
