Department of Integrative Medicine and Neurobiology, Institutes of Integrative Medicine, School of Basic Medical Sciences, Institutes of Brain Science, Brain Science Collaborative Innovation Center, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China.
Life Sci. 2020 Oct 1;258:118198. doi: 10.1016/j.lfs.2020.118198. Epub 2020 Aug 3.
Trigeminal neuralgia is characterized by extensive spreading of pain, referred to as ectopic pain, which describes the phenomenon of the pain passing from the injured regions to uninjured regions. Patients with orofacial pain often show no response to commonly used analgesics, and the exact mechanism of ectopic pain remains unclear, which restricts the development of specific drugs. The present review aims to summarize the contribution of the two families of transmembrane proteins, connexins (Cxs) and pannexins (Panxs), to the induction and spreading of orofacial pain and to provide potential targets for orofacial pain treatment. Cxs and Panxs have recently been shown to play essential roles in intercellular signal propagation in sensory ganglia, and previous studies have provided evidence for the contribution of several subtypes of Cxs and Panxs in various orofacial pain models. Upregulation of the expression of Cxs and Panxs in the trigeminal ganglia is observed in most cases after trigeminal injury, and regulating their expression or activity can improve pain-like behaviors in animals. It is speculated that after trigeminal injury, pain-related signals are transmitted to adjacent neurons and satellite glial cells in the trigeminal ganglia directly through gap junctions and simultaneously through hemichannels and pannexons through both autocrine and paracrine mechanisms. This review highlights recent discoveries in the regulation of Cxs and Panxs in different orofacial pain models and presents a hypothetical mechanism of ectopic pain in trigeminal neuralgia. In addition, the existing problems in current research are discussed.
三叉神经痛的特点是疼痛广泛扩散，称为异位疼痛，描述了疼痛从受伤区域传递到未受伤区域的现象。口腔面部疼痛患者通常对常用的镇痛药没有反应，而异位疼痛的确切机制尚不清楚，这限制了特定药物的发展。本综述旨在总结两种跨膜蛋白家族，连接蛋白（Cxs）和 Pannexin（Panxs）对口腔面部疼痛的诱导和扩散的贡献，并为口腔面部疼痛治疗提供潜在的靶点。Cxs 和 Panxs 最近被证明在感觉神经节中对细胞间信号传递起着重要作用，先前的研究为几种 Cxs 和 Panxs 亚型在各种口腔面部疼痛模型中的作用提供了证据。在大多数情况下，三叉神经损伤后三叉神经节中 Cxs 和 Panxs 的表达上调，调节其表达或活性可以改善动物的疼痛样行为。据推测，三叉神经损伤后，疼痛相关信号通过缝隙连接直接传递到三叉神经节中的相邻神经元和卫星神经胶质细胞，同时通过半通道和 Pannexon 通过自分泌和旁分泌机制传递到相邻神经元和卫星神经胶质细胞。本综述强调了最近在不同口腔面部疼痛模型中 Cxs 和 Panxs 调节方面的发现，并提出了三叉神经痛中异位疼痛的假设机制。此外，还讨论了当前研究中存在的问题。
