Jia Ze-jun, Wu Fei-xiang, Huang Qing-hai, Liu Jian-min
Department of Neurosurgery, Second Military Medical University, Shanghai, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2012 Apr;34(2):168-73. doi: 10.3881/j.issn.1000-503X.2012.02.013.
Activation of microglia plays a vital role in the initiation and maintenance of specific neuropathic pain states. By activating microglia in central nervous system, Toll-like receptor 4 (TLR4) can promote the release of proinflammatory cytokines and neuroactive compounds, participate in the initiation and maintenance of neuropathic pain, and trigger the opiate side effects. Therefore, TLR4 may be a potential therapeutic target for neuropathic pain. Inhibition of TLR4 has shown some biological effects in neuropathic pain models and ibudilast (the TLR4 pathway-inhibiting agent) has been approved for for phase 2 clinical trials. This article briefly reviews the structure, function, and mechanism of TLR4 as well as the development of TLR4-targeted drugs.
小胶质细胞的激活在特定神经性疼痛状态的起始和维持中起着至关重要的作用。通过激活中枢神经系统中的小胶质细胞，Toll样受体4（TLR4）可促进促炎细胞因子和神经活性化合物的释放，参与神经性疼痛的起始和维持，并引发阿片类药物的副作用。因此，TLR4可能是神经性疼痛的一个潜在治疗靶点。在神经性疼痛模型中，抑制TLR4已显示出一些生物学效应，异丁司特（TLR4通路抑制剂）已获批进入2期临床试验。本文简要综述了TLR4的结构、功能和机制以及靶向TLR4药物的研发情况。
