Role of Neuron-Glial Interaction Mediated by IL-1β in Ectopic Tooth Pain
Role of Neuron-Glial Interaction Mediated by IL-1β in Ectopic Tooth Pain
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DOI：
10.1177/0022034517741253
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发表时间：
2018-04-01
影响因子：
7.6
通讯作者：
Iwata, K.
中科院分区：
文献类型：
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作者：
Komiya, H.;Shimizu, K.;Iwata, K.
尽管许多报道表明，牙髓炎症后口面部区域会出现异位疼痛，这常常导致牙髓炎患者的误诊和不适当的治疗，但其确切机制仍不清楚。在本研究中，我们假设三叉神经节（TG）中白细胞介素1β（IL-1β）介导的卫星胶质细胞和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口面部疼痛。通过分析将辣椒素注入上颌第二磨牙牙髓引起的二腹肌肌电图（D-EMG）活性，以评估伤害性反射，与注射盐水的大鼠相比，上颌第一磨牙（MI）炎症的大鼠的二腹肌肌电图（D-EMG）活性显着增加。 MI 牙髓炎后，在 TG 中第二磨牙神经元周围激活的卫星胶质细胞中观察到 connexin43 (Cx43)（一种含有间隙连接的蛋白质）的表达显着增加。 TG 中每日施用 Gap26（一种 Cx43 模拟肽和抑制剂）可显着抑制 MI 牙髓炎症后辣椒素诱导的 D-EMG 活性的增强以及被胶质原纤维酸性蛋白免疫反应性 (IR) + Cx43-IR 细胞包围的氟金 (FG) 标记细胞的百分比 (P < 0.01)。 MI牙髓炎症后，胶质原纤维酸蛋白-IR+IL-1β-IR细胞、IL-I I型受体-FG标记的IR细胞和FG标记的TRPV1-IR细胞包围的FG标记细胞的百分比显着增加（P < 0.01）。每日向 TG 中施用 IL-1ra（一种 IL-1 受体拮抗剂）可显着降低 MI 牙髓炎症后辣椒素诱导的 D-EMG 活性的增强以及 FG 标记的 TRPV1-IR 神经元的百分比（P < 0.01）。目前的研究结果表明，牙髓炎症后，TG 中的卫星胶质细胞通过由 Cx43 组成的激活间隙连接被激活，从而通过 IL-1 β 机制导致远程神经元过度激活，并导致邻近牙齿的异位牙髓疼痛。
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 1 beta (IL-1 beta) 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 (MI) 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 MI 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 MI pulp inflammation (P < 0.01). The percentage of FG-labeled cells encircled by glial fibrillary acid protein-IR + IL-1 beta-IR cells, IL-I type I receptor-IR cells labeled with FG, and TRPV1-IR cells labeled with FG significantly increased after MI 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 MI 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-1 beta mechanisms and results in ectopic tooth pulp pain in the adjacent tooth.