黄藤素对三叉神经节P2X7受体介导的三叉神经痛的作用研究

Trigeminal neuralgia (TN) is one of the most intense forms of facial pain characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution, and is the key problem of clinic pain treatment. Trigeminal ganglion (TG) plays an important role in the formation of TN. Our preliminary experiments showed that the expression of P2X7 receptor in TG of TN rats is obviously higher than that in the control rats, indicating that P2X7 receptor of TG is involved in pain transmission of TN. In addition, the preliminary experiments showed that the expression of calcitonin gene related peptide (CGRP), proinflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) increased significantly compared to normal rats. Preliminary experiments also found that treatment of traditional Chinese medicine palmatine alleviated the mechanical hyperalgesia of TN rats, and significantly decreased the expression of up-regulated P2X7 receptor, CGRP, IL-1β and TNF-α in TG of TN rats. The aim of the project is to study the effects of palmatine on the expression of P2X7 receptor of TG in TN rats, and to find its possible mechanism, and provide new drug and experimental evidences for the prevention and treatment of TN.

三叉神经痛是三叉神经分布区域突发的刀割样阵痛为主要特征的严重的面部疼痛，是临床疼痛治疗的难点。三叉神经节(TG)在三叉神经痛形成中具有重要作用。预实验显示三叉神经痛大鼠TG嘌呤2X7受体(P2X7)受体的表达明显高于对照组，表明TG的P2X7受体参与三叉神经痛大鼠的痛觉传递。此外，预实验还发现三叉神经痛大鼠TG中降钙素基因相关肽(CGRP)、前炎症因子白细胞介素1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的表达和正常大鼠相比也显著升高。同时，预实验发现中药黄藤素处理能缓解三叉神经痛大鼠的机械痛敏，显著降低TG中高表达的P2X7受体、CGRP、IL-1β和TNF-α。本项目拟研究黄藤素对三叉神经痛大鼠TG的P2X7受体表达的影响及可能机理，为三叉神经痛防治提供新的药物和实验基础。

三叉神经痛是三叉神经分布区域突发的刀割样阵痛为主要特征的重度面部疼痛，是临床疼痛治疗的难点。三叉神经节(TG)在三叉神经痛形成中具有重要作用，并且TG中表达的P2X7受体和慢性痛密切相关。本研究采用慢性压迫性损伤眶下神经建立三叉神经痛大鼠动物模型进行观察，结果表明三叉神经痛大鼠TG中P2X7受体的表达明显高于假手术组，表明TG的P2X7受体参与了三叉神经痛大鼠的痛觉传递。此外，我们还发现三叉神经痛大鼠TG中P2X4受体、降钙素基因相关肽(CGRP)、脑源性神经营养因子（BDNF）、前炎症因子白细胞介素1β (IL-1β)和肿瘤坏死因子-α (TNF-α)的表达和假手术组大鼠相比也显著升高。同时，实验结果发现中药黄藤素处理能缓解三叉神经痛大鼠的机械痛敏，显著降低TG中高表达的P2X7受体、P2X4受体、BDNF、CGRP、IL-1β和TNF-α等分子水平。此外，本研究通过构建P物质诱导的神经细胞和卫星胶质细胞损伤疼痛模型开展细胞水平研究。研究发现P2X7受体和P2X4受体参与了P物质诱导的神经细胞和卫星胶质细胞损伤，同时观察到黄藤素对细胞损伤的有一定保护作用。黄藤素可能通过下调P2X7受体和P2X4受体表达，抑制炎症水平，从而参与P物质诱导的细胞疼痛模型中的病理变化，对细胞损伤产生保护作用。本研究结果表明黄藤素的镇痛机制值得深入研究，黄藤素有可能是一个有效的三叉神经痛或相关的慢性神经病理性疼痛的治疗药物。因此，本研究为三叉神经痛防治提供了新的药物和实验基础，同时也为慢性痛的治疗提供了新思路