摘要目的:评价离子型嘌呤受体4(P2X4R)在大鼠三叉神经痛维持中的作用及与p38丝裂原活化蛋白激酶(p38 MAPK)/脑源性神经营养因子(BDNF)信号通路的关系。方法:清洁级健康成年雄性SD大鼠48只，体质量190~230 g，2~3月龄，采用随机数字表法分为4组( n＝12)：假手术组(S组)、三叉神经痛组(TN组)、三叉神经痛+二甲基亚砜组(TN+DMSO组)和三叉神经痛+P2X4R特异性拮抗剂5-BDBD组(TN+5-BDBD组)。采用三叉神经眶下支慢性缩窄术制备三叉神经痛模型。于造模后3、7、10和14 d时，TN+5-BDBD组鞘内注射5 μg/μl 5-BDBD 10 μl，TN+DMSO组鞘内注射2%二甲基亚砜10 μl。于造模前1 d、造模后1、3、7、10、14和28 d(T 0~6)时测定面部机械痛阈(MWT)。末次行为学测定结束后，处死大鼠取三叉神经节，采用Western blot法检测P2X4R、p38 MAPK、磷酸化p38 MAPK(p-p38 MAPK)和BDNF的表达，采用ELISA法检测TNF-α、IL-1β和IL-6的含量。 结果:与S组比较，TN组T 1~6时MWT降低，三叉神经节P2X4R、p-p38MAPK和BDNF表达上调，TNF-α、IL-1β和IL-6含量升高( P<0.05)；与TN组比较，TN+5-BDBD组T 3~6时MWT升高，三叉神经节P2X4R、p-p38 MAPK和BDNF表达下调，TNF-α、IL-1β和IL-6含量降低( P<0.05)，TN+DMSO组上述指标差异无统计学意义( P>0.05)。 结论:P2X4R参与了大鼠三叉神经痛的维持，可能与激活p38 MAPK/BDNF信号通路，增加炎性介质释放有关。

abstractsObjective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.