Guo Sheng-Jie, Shi Yu-Qin, Zheng Ya-Nan, Liu Hui, Zheng Yi-Li
Department of Sport Rehabilitation, Shanghai University of Sport, 399 Changhai Road, Yangpu District, Shanghai, China.
Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, China.
Mol Neurobiol. 2025 Feb;62(2):2561-2572. doi: 10.1007/s12035-024-04424-w. Epub 2024 Aug 13.
Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.
神经性疼痛（NP）是一种由躯体感觉神经系统损伤或疾病引起的慢性疼痛，也可能直接由疾病导致。它常表现出如自发痛、痛觉过敏和感觉异常等临床特征。目前已知电压门控钙离子通道（VGCCs）与NP的发生发展密切相关，尤其是α2δ亚基。α2δ亚基是VGCCs的一个调节亚基。它主要存在于脑和外周神经系统，特别是神经细胞中，在调节突触前和突触后功能方面发挥着关键作用。此外，α2δ亚基通过与VGCC相关亚基结合来促进其表达和定位，从而影响神经元兴奋和疼痛信号传导。α2δ亚基作为抗癫痫药物加巴喷丁和普瑞巴林的靶点，被广泛应用于NP的治疗。虽然药物治疗是NP的治疗方法之一，但其临床应用因药物治疗引起的不良反应而受到限制。因此，需要对治疗靶点α2δ亚基进行进一步研究，并尝试获得一种有效缓解NP且无副作用的治疗方法。本综述描述了目前关于α2δ亚基在感知和调节NP功能方面的相关知识。
