A-317491对P2X3受体介导的三叉神经痛的作用研究

目的:探究P2X3受体特异性拮抗剂A-317491对三叉神经痛的作用影响.方法:慢性压迫性损伤大鼠眶下神经(CCI-ION)建立大鼠三叉神经痛动物模型,应用von Frey细丝法测试机械刺激反应阈值,观察A-317491对三叉神经痛(TN)大鼠机械刺激反应阈值的影响.结合免疫组织化学、原位杂交、蛋白印迹、PT-PCR等方法观察大鼠三叉神经节(TG)中P2X3受体的表达变化.结果:术后14d,Ⅲ组(TN模型组)和Ⅰ组(生理盐水对照组)、Ⅱ组(假手术组)、Ⅳ组(TN模型+A-317491干预组)相比较,大鼠手术侧眶下神经面部感觉区域机械痛敏阈值明显降低(P＜0.01),大鼠TG中P2X3受体表达明显升高(P＜0.01);Ⅰ、Ⅱ、Ⅳ组之间相比,大鼠手术侧眶下神经面部感觉区域机械痛敏阈值差异没有显著性;Ⅳ组TG中P2X3受体的表达较Ⅲ组低(P＜0.01).结论:P2X3受体涉及到三叉神经痛,P2X3受体特异性拮抗剂A-317491对P2X3受体介导的三叉神经痛有一定抑制作用.

The Role of A-317491 in Trigeminal Neuralgia Mediated by P2X3 Receptor

Objective: To explore the role of A-317491,a specific antagonist of P2X3 receptor in trigeminal neuralgia.Methods: The trigeminal neuralgia rat model(a chronic constriction injury of the infraorbital branch of the trigeminal nerve,CCI-ION) was established.The mechanical hyperalgesia threshold of trigeminal neuralgia(TN) rats was tested by the von Frey filaments.The change of the expression of P2X3 receptors in rats’ trigeminal ganglion(TG) was detected with immunohistochemical staining,in situ hybridization,Western Blot,RT-PCR.Results: 14 days after operation,compared withⅠ group(saline control group),Ⅱ group(sham operation group) or Ⅳ group(TN model + A-317491 intervention group),Ⅲ group(TN model group) had a significant decrease of mechanical hyperalgesia threshold in the territory of ligated infraorbital nerve(P<0.01),and an obvious increase in expression of P2X3 receptor in rats’ TG(P<0.01);there is no significant differences of mechanical hyperalgesia threshold amongⅠ,Ⅱand Ⅳ group.The expression of P2X3 receptor of TG in Ⅳ group was lower than that in Ⅲ group(P<0.01).Conclusion: P2X3 receptor may play a key role in the pain transmitting of trigeminal neuralgia,and specific antagonist of P2X3 receptor A-317491 has inhibitory effect of trigeminal neuralgia.