Department of Neurology, The First Branch of The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Neuroimmunol. 2023 Aug 15;381:578118. doi: 10.1016/j.jneuroim.2023.578118. Epub 2023 Jun 1.
Migraines are a considerable social problem and economic burden worldwide. Current acute treatments are based on inhibiting meningeal neurogenic inflammation which has poor results in some patients, whereas the site of action of prophylactic medicines are unknown; therefore, exploring new treatment mechanisms and methods is increasingly needed. Recent evidence suggests that microglia and microglia-mediated neuroinflammation are important in migraine pathogenesis. In the cortical spreading depression (CSD) migraine model, microglia were activated after multiple CSD stimulations, suggesting that microglial activation may be associated with recurrent attacks of migraine with aura. In the nitroglycerin-induced chronic migraine model, the microglial response to extracellular stimuli leads to the activation of surface purine receptors P2X4、P2X7、P2Y12, which mediate signal transduction through intracellular signalling cascades, such as the BDNF/TrkB, NLRP3/IL-1β and RhoA/ROCK signalling pathways, and release inflammatory mediators and cytokines that enhance pain by increasing the excitability of nearby neurons. Inhibition of the expression or function of these microglial receptors and pathways inhibits the abnormal excitability of TNC (trigeminal nucleus caudalis) neurons and intracranial as well as extracranial hyperalgesia in migraine animal models. These findings suggest that microglia may be central in migraine recurrent attacks and a potential target for the treatment of chronic headaches.
偏头痛是全球范围内一个相当严重的社会问题和经济负担。目前的急性治疗方法基于抑制脑膜神经源性炎症，而这种方法在一些患者中效果不佳，而预防药物的作用部位尚不清楚；因此，越来越需要探索新的治疗机制和方法。最近的证据表明，小胶质细胞和小胶质细胞介导的神经炎症在偏头痛发病机制中起重要作用。在皮质扩散性抑制（CSD）偏头痛模型中，多次 CSD 刺激后小胶质细胞被激活，这表明小胶质细胞的激活可能与有先兆偏头痛的反复发作有关。在硝酸甘油诱导的慢性偏头痛模型中，小胶质细胞对细胞外刺激的反应导致表面嘌呤受体 P2X4、P2X7、P2Y12 的激活，这些受体通过细胞内信号转导途径（如 BDNF/TrkB、NLRP3/IL-1β和 RhoA/ROCK 信号通路）介导信号转导，并释放炎症介质和细胞因子，通过增加附近神经元的兴奋性来增强疼痛。抑制这些小胶质细胞受体和途径的表达或功能可抑制偏头痛动物模型中 TNC（三叉神经尾核）神经元的异常兴奋性和颅内及颅外痛觉过敏。这些发现表明，小胶质细胞可能在偏头痛的反复发作中起核心作用，是治疗慢性头痛的潜在靶点。
