Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, PR China.
Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China; Department of Oral and Maxillofacial Surgery, Qingdao Municipal Hospital, Shandong, PR China.
Neurosci Lett. 2019 Aug 10;707:134301. doi: 10.1016/j.neulet.2019.134301. Epub 2019 May 29.
We previously demonstrated that sodium channel 1.7 (Nav1.7) in trigeminal ganglion (TG) was a critical factor in temporomandibular joint (TMJ) inflammation-induced hypernociception, but the mechanism underlying inflammation-induced upregulation of Nav1.7 remained unclear. Glial-neuron interaction plays a critical role in pain process and connexin 43 (Cx43), a gap junction protein expressed in satellite glial cells (SGCs) has been shown to play an important role in several pain models. In the present study, we investigate the role of Cx43 in TMJ inflammation-induced hypernociception and its possible impact on neuronal Nav1.7. We induced TMJ inflammation in rats by injecting complete Freund's adjuvant (CFA) into TMJ and observed a decrease in head withdraw threshold after 24 h. Electron microscopy showed morphological alterations of SGCs in TMJ-inflamed rats. The expression of Cx43, glial fibrillary acidic protein (GFAP), and Nav1.7 increased greatly compared with controls. In addition, pretreatment with Cx43 blockers in TMJ-inflamed rats could alleviate mechanical hypernociception, inhibit SGCs activation and IL-1βrelease, and thus block the upregulation of Nav1.7. These findings indicate that the propagation of SGCs activation via Cx43 plays a critical role in Nav1.7-involved mechanical hypernociception induced by TMJ inflammation.
我们之前的研究表明，三叉神经节（TG）中的钠离子通道 1.7（Nav1.7）是颞下颌关节（TMJ）炎症引起的痛觉过敏的关键因素，但炎症引起 Nav1.7 上调的机制尚不清楚。胶质细胞-神经元相互作用在疼痛过程中起着关键作用，间隙连接蛋白 43（Cx43）在卫星胶质细胞（SGC）中表达，已被证明在几种疼痛模型中发挥重要作用。在本研究中，我们研究了 Cx43 在 TMJ 炎症引起的痛觉过敏中的作用及其对神经元 Nav1.7 的可能影响。我们通过向 TMJ 注射完全弗氏佐剂（CFA）诱导 TMJ 炎症，并在 24 小时后观察到头撤回阈值降低。电子显微镜显示 TMJ 炎症大鼠 SGC 的形态改变。与对照组相比，Cx43、胶质纤维酸性蛋白（GFAP）和 Nav1.7 的表达大大增加。此外，在 TMJ 炎症大鼠中预先使用 Cx43 阻滞剂可以减轻机械性痛觉过敏，抑制 SGC 激活和 IL-1β释放，从而阻断 Nav1.7 的上调。这些发现表明，通过 Cx43 传播的 SGC 激活在 TMJ 炎症引起的 Nav1.7 参与的机械性痛觉过敏中起着关键作用。
