1 Department of Endodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
2 Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
J Dent Res. 2018 Apr;97(4):467-475. doi: 10.1177/0022034517741253. Epub 2017 Nov 13.
Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation. The digastric muscle electromyogram (D-EMG) activity elicited by capsaicin administration into the maxillary second molar tooth pulp was analyzed to evaluate the noxious reflex and was significantly increased in rats with inflammation of the maxillary first molar (M1) versus rats injected with saline. A significant increase in the expression of connexin43 (Cx43), a gap junction containing protein, was observed in activated satellite glial cells surrounding second molar-innervating neurons in the TG after M1 pulpitis. Daily administration of Gap26, a Cx43 mimetic peptide and inhibitor, in the TG significantly suppressed the enhancement of capsaicin-induced D-EMG activity and the percentage of Fluoro-Gold (FG)-labeled cells encircled by glial fibrillary acid protein-immunoreactive (IR) + Cx43-IR cells after M1 pulp inflammation ( P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1β-IR cells, IL-1 type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after M1 pulp inflammation ( P < 0.01). Daily administration of IL-1ra, an IL-1 receptor antagonist, into the TG significantly reduced the enhancement of capsaicin-induced D-EMG activity and the percentage of TRPV1-IR neurons labeled with FG after M1 pulp inflammation ( P < 0.01). The present findings suggest that satellite glial cell is activated in the TG via activated gap junctions composed of Cx43 following tooth pulp inflammation, which leads to the hyperactivation of remote neurons via IL-1β mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.
虽然许多报告表明，牙髓炎症后会在口腔颌面部区域产生异位痛，这常常导致牙髓病患者的误诊和不当治疗，但确切的机制尚不清楚。在本研究中，我们假设三叉神经节（TG）中卫星胶质细胞和神经元之间由白细胞介素 1β（IL-1β）介导的功能相互作用与牙髓炎症相关的异位口腔疼痛有关。通过向第二磨牙牙髓内给予辣椒素来分析二腹肌肌电图（D-EMG）活动，以评估伤害性反射，结果发现与生理盐水注射组相比，上颌第一磨牙（M1）炎症大鼠的 D-EMG 活动显著增加。在 M1 牙髓炎后，TG 中第二磨牙传入神经元周围激活的卫星胶质细胞中，连接蛋白 43（Cx43）的表达显著增加，Cx43 是一种间隙连接蛋白。每天在 TG 中给予 Cx43 模拟肽和抑制剂 Gap26，可显著抑制 M1 牙髓炎症后辣椒素诱导的 D-EMG 活动增强和被神经胶质纤维酸性蛋白免疫反应性（IR）+ Cx43-IR 细胞环绕的 Fluoro-Gold（FG）标记细胞的百分比（P<0.01）。M1 牙髓炎症后，被神经胶质纤维酸性蛋白-IR+IL-1β-IR 细胞、FG 标记的 IL-1 型受体-IR 细胞和 FG 标记的 TRPV1-IR 细胞环绕的 FG 标记细胞的百分比显著增加（P<0.01）。每天在 TG 中给予白细胞介素 1 受体拮抗剂 IL-1ra 可显著降低 M1 牙髓炎症后辣椒素诱导的 D-EMG 活动增强和 FG 标记的 TRPV1-IR 神经元的百分比（P<0.01）。本研究结果表明，牙髓炎症后，通过由 Cx43 组成的激活的缝隙连接，TG 中的卫星胶质细胞被激活，这导致通过 IL-1β 机制使远程神经元过度激活，并导致相邻牙齿的牙髓异位痛。
