Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.
Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.
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DOI：
10.1177/1744806916633704
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Iwata K
中科院分区：
文献类型：
--
作者：
Kaji K;Shinoda M;Honda K;Unno S;Shimizu N;Iwata K
临床上，下颌神经纤维损伤可引起持续性异位疼痛，这种疼痛可扩散到由未损伤的三叉神经分支支配的广大口面区。然而，这种持续异位口面部疼痛的确切机制尚不清楚。本研究旨在探讨三叉神经节连接蛋白43在大鼠下肺泡神经损伤所致须垫皮肤机械超敏反应中的作用。在这里，我们检查了下肺泡神经损伤后口面机械敏感性的变化。此外，我们还研究了连接蛋白43在三叉神经节中的表达变化及其在三叉神经节中的定位。此外，我们通过使用选择性间隙连接阻滞剂（Gap27）研究了连接蛋白43在机械异常性疼痛中的功能意义。下肺泡神经损伤后，须垫皮肤和上眼睑皮肤出现持久的机械异常性疼痛，三叉神经节卫星神经胶质细胞激活。连接蛋白43在支配须垫皮肤的三叉神经节神经元周围活化的卫星胶质细胞中表达，下肺泡神经损伤后连接蛋白43的表达显著升高。在三叉神经节中施用Gap27可显著降低须垫皮肤的卫星胶质细胞活化和机械超敏反应。此外，在下泡神经损伤后，支配须垫皮肤的三叉神经节神经元周围的卫星神经胶质细胞的显著激活表明，卫星神经胶质细胞的激活对三叉神经节痛觉神经元的兴奋性有重要影响。这些发现表明，卫星胶质细胞激活通过由连接蛋白43组成的间隙连接在三叉神经节中传播，在下肺泡神经损伤后须垫皮肤的异位机械超敏反应中起关键作用。
Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27). Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons. These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are composed of connexin 43, plays a pivotal role in ectopic mechanical hypersensitivity in whisker pad skin following inferior alveolar nerve injury.