Objective: To study the role of P2X4 receptor (P2X4R) in the pathogenesis of chronic migraine (CM) by observing the changes of P2X4R expression in trigeminal nucleus caudalis (TNC) in a rat model of chronic migraine. Methods: Male Sprague-Dawley rats were randomly divided into 5 groups: control (n = 12), CM (n = 12), CM + PBS (n = 6), CM + TNP-ATP 30 (n = 6), CM + TNP-ATP 60 nmol (n = 6). The inflammatory soup (IS) was repeatedly infused onto the dura matter in awake rats to establish the rat model of chronic migraine. Mechanical pain threshold in periorbital and hindpaw regions was determined with von Frey test. Western blot was used to detect the expression of P2X4R and c-Fos. Localization of P2X4R in TNC was detected with immunofluorescence methods. Results: Immunofluorescence staining showed that P2X4R was mainly expressed in microglia in TNC. Compared to control group, the pain threshold in CM group in face and hindpaw regions was remarkably decreased (P < 0.01), while the expression of P2X4R and c-Fos, a marker of neuronal activation, was significantly increased (P < 0.05). Mechanical pain threshold in CM group in periorbital and hindpaw was markedly increased after administration of TNP-ATP (P < 0.05), while the expression of c-Fos was significantly reduced (P < 0.05). Conclusion: The upregulation of microglia P2X4R in TNC might be involved in the pathogenesis of chronic migraine, which might be related to the activation of neurons in TNC.%目的:观察P2X4受体 (P2X4 receptor, P2X4R) 在慢性偏头痛 (chronic migraine, CM) 大鼠三叉神经脊束尾核 (trigeminal nucleus caudalis, TNC) 的表达变化,探讨其在CM中的作用.方法:SD雄性大鼠随机分为5组,对照组 (n = 12)、模型组 (n = 12)、模型+溶剂组 (n = 6)、模型+TNP-ATP 30 nmol组 (n = 6)、模型+TNP-ATP 60 nmol组 (n = 6).硬脑膜反复滴注 "炎性汤" (inflammatory soup, IS) 建立CM模型.von Frey test检测眶周及后足机械痛阈值,Western blot检测P2X4R及神经元激活标志蛋白c-Fos的表达,免疫荧光检测P2X4R定位情况.结果:荧光染色显示P2X4R主要表达于TNC小胶质细胞.与对照组相比,模型组大鼠眶周及后足痛阈值显著降低 (P < 0.01),P2X4R及c-Fos表达量显著上调 (P < 0.05).给予P2X4R抑制剂TNP-ATP后,大鼠眶周及后足痛阈值显著升高 (P < 0.05), c-Fos表达量显著降低 (P < 0.05).结论:TNC小胶质细胞P2X4R表达上调,可能通过影响神经元的激活从而参与CM发病过程.
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