Komiya Hiroki, Shimizu Kohei, Ishii Kae, Kudo Hiroshi, Okamura Teinosuke, Kanno Kohei, Shinoda Masamichi, Ogiso Bunnai, Iwata Koichi
Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry.
Department of Endodontics, Nihon University School of Dentistry.
J Oral Sci. 2018;60(4):493-499. doi: 10.2334/josnusd.17-0452.
Pulpitis often causes referred pain in opposing teeth. However, the precise mechanism underlying ectopic pain associated with tooth-pulp inflammation remains unclear. We performed the present study to test the hypothesis that functional interactions between satellite glial cells (SGCs) and trigeminal ganglion (TG) neurons are involved in ectopic orofacial pain associated with tooth-pulp inflammation. Digastric muscle electromyograph (D-EMG) activity elicited by administration of capsaicin into the upper second molar pulp (U2) was analyzed to evaluate noxious reflex responses. D-EMG activity was significantly increased in rats with lower first molar (L1) inflammation relative to saline-treated rats. Significantly increased expression of glial fibrillary acid protein (GFAP), a marker of activated glial cells, and connexin 43 (Cx43), a gap-junction protein, was observed in activated SGCs surrounding U2-innervating TG-neurons after L1-pulp inflammation. Daily administration of Gap26, a Cx43-inhibiting mimetic peptide, into the TG significantly suppressed capsaicin-induced D-EMG activity enhancement and reduced the percentage of fluorogold-labeled (U2-innervated) cells that were surrounded by GFAP-immunoreactive (IR) and Cx43-IR cells after L1-pulp inflammation. These findings indicate that tooth-pulp inflammation induces SGC activation and subsequent spread of SGC activation in the TG via Cx43-containing gap junctions. Thus, remote neuron excitability becomes enhanced in the TG following tooth-pulp inflammation, resulting in ectopic tooth-pulp pain in the contralateral tooth.
牙髓炎常导致对颌牙出现牵涉痛。然而，与牙髓炎症相关的异位疼痛的确切机制仍不清楚。我们开展了本研究，以检验以下假设：卫星神经胶质细胞（SGCs）与三叉神经节（TG）神经元之间的功能相互作用参与了与牙髓炎症相关的异位性口面部疼痛。通过分析将辣椒素注入上颌第二磨牙牙髓（U2）所引发的二腹肌肌电图（D-EMG）活动，来评估伤害性反射反应。与生理盐水处理的大鼠相比，第一磨牙（L1）发生炎症的大鼠的D-EMG活动显著增加。在L1牙髓炎症后，在支配U2的TG神经元周围被激活的SGCs中，观察到胶质纤维酸性蛋白（GFAP，一种激活的神经胶质细胞标志物）和连接蛋白43（Cx43，一种间隙连接蛋白）的表达显著增加。每天向TG注射Cx43抑制模拟肽Gap26，可显著抑制辣椒素诱导的D-EMG活动增强，并降低L1牙髓炎症后被GFAP免疫反应性（IR）和Cx43-IR细胞包围的荧光金标记（由U2支配）细胞的百分比。这些发现表明，牙髓炎症通过含Cx43的间隙连接诱导SGC激活以及随后SGC激活在TG中的扩散。因此，牙髓炎症后TG中的远程神经元兴奋性增强，导致对侧牙齿出现异位性牙髓疼痛。
