Hong Chaoli, Hayashi Yoshinori, Hitomi Suzuro, Kurisu Ryoko, Urata Kentaro, Shibuta Ikuko, Toyofuku Akira, Iwata Koichi, Shinoda Masamichi
Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Department of Physiology, Nihon University School of Dentistry, 1-8-13, Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Neurosci Res. 2023 Mar;188:68-74. doi: 10.1016/j.neures.2022.10.009. Epub 2022 Nov 2.
Glial cells, such as microglia and astrocytes, in the trigeminal spinal subnucleus caudalis (Vc) are activated after trigeminal nerve injury and interact with Vc neurons to contribute to orofacial neuropathic pain. Complement C1q released from microglia has been reported to activate astrocytes and causes orofacial mechanical allodynia. However, how C1q-induced phenotypic alterations in Vc astrocytes are involved in orofacial pain remains to be elucidated. Intracisternal administration of C1q caused mechanical allodynia in the whisker pad skin and concurrent significant upregulation of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 in the Vc. Immunohistochemical analyses clarified that C1q induces a significant increase in the cytokine interleukin (IL)-1β, predominantly in Vc astrocytes and partially in Vc microglia. The number of c-Fos-positive neurons in the Vc increased significantly in response to C1q. IL-1 receptor antagonist (IL-1Ra) was used to analyze the involvement of IL-1β in C1q-induced mechanical allodynia. Intracisternal administration of IL-1Ra ameliorated C1q-induced orofacial mechanical allodynia. The present findings suggest that IL-1β released from activated astrocytes and microglia in the Vc mediates C1q-induced orofacial pain.
三叉神经脊束核尾侧亚核（Vc）中的神经胶质细胞，如小胶质细胞和星形胶质细胞，在三叉神经损伤后被激活，并与Vc神经元相互作用，导致口面部神经性疼痛。据报道，小胶质细胞释放的补体C1q可激活星形胶质细胞并引起口面部机械性异常性疼痛。然而，C1q诱导的Vc星形胶质细胞表型改变如何参与口面部疼痛仍有待阐明。脑池内注射C1q可导致触须垫皮肤出现机械性异常性疼痛，并同时使Vc中的胶质纤维酸性蛋白和离子钙结合衔接分子1显著上调。免疫组织化学分析表明，C1q可诱导细胞因子白细胞介素（IL）-1β显著增加，主要在Vc星形胶质细胞中，部分在Vc小胶质细胞中。Vc中c-Fos阳性神经元的数量因C1q而显著增加。使用白细胞介素-1受体拮抗剂（IL-1Ra）来分析IL-1β在C1q诱导的机械性异常性疼痛中的作用。脑池内注射IL-1Ra可改善C1q诱导的口面部机械性异常性疼痛。目前的研究结果表明，Vc中活化的星形胶质细胞和小胶质细胞释放的IL-1β介导了C1q诱导的口面部疼痛。
