背根神经节CXCR4在大鼠切口痛中的作用

Role of CXCR4in dorsal root ganglia in incisional pain in rats

目的 评价背根神经节趋化因子CXC亚族受体4 ( CXCR4)在大鼠切口痛中的作用.方法 取鞘内置管成功的雄性SD大鼠32只,体重250~300 g,7~10周龄,采用随机数字表法分为4组(n=8):假手术组(S组)、CXCR4拮抗剂AMD3100+假手术组( A+S组)、切口痛( I组)和CXCR4拮抗剂AMD3100+切口痛组( A+I组). A+S组预先鞘内注射 AMD3100 20 μg (溶于生理盐水10 μl),30 min后行足底消毒,不做切口;I组制备切口痛模型;A+I组预先鞘内注射AMD3100 20 μg (溶于生理盐水10 μl),30 min后制备切口痛模型.于造模前24 h(T0)、造模后2、4、8、16和24 h(T1-5)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL).最后1次测定痛阈后处死大鼠,取L4,5节段背根神经节,采用 Western blot法测定 CXCR4、磷酸化细胞外调节蛋白激酶(p-ERK)和总 ERK(t-ERK)的表达水平.结果 与S组比较,I组和A+I组T1-5时MWT降低,TWL缩短,I组背根神经节CXCR4和p-ERK表达上调(P<0. 05),t-ERK表达差异无统计学意义,A+I组背根神经节CXCR4、p-ERK和t-ERK表达差异无统计学意义,A+S组上述各指标差异无统计学意义( P>0. 05).与I组比较,A+I组T1-5时MWT升高,TWL延长,背根神经节CXCR4和p-ERK表达下调( P<0. 05),t-ERK表达差异无统计学意义(P>0. 05).结论 背根神经节CXCR4参与大鼠切口痛的过程,其机制可能与激活ERK信号通路有关.

Objective To evaluate the role of C-X-C chemokine receptor type 4(CXCR4)in the dorsal root ganglia (DRG)in incisional pain in rats.Methods Thirty-two male Sprague-Dawley rats, aged 7-10weeks,weighing 250-300g,in which intrathecal catheters were successfully implanted,were divided into 4groups (n=8each)using a random number table method:sham operation group (group S), CXCR4antagonist AMD3100plus sham operation group (group A+S),incisional pain group (group I)and CXCR4antagonist AMD3100plus incisional pain group (group A+I).Rats were anesthetized with sevoflurane.AMD310020μg (in 10ILl of normal saline)was intrathecally injected,and no incision was made 30 min later in group A+S.A 1-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the left hindpaw in group I.AMD310020μg (in 10μl of normal saline)was intrathecally injected,and 30min later the model of incisional pain was established in group A+I.The mechanical paw withdrawal threshold (MWT)and thermal paw withdrawal latency (TWL)were measured at 24h before surgery and 2,4,8,16and 24h after surgery.The rats were sacrificed after the last measurement of pain threshold and the DRGs of the lumbar segment (L4-6)were removed for detecting the expression of CXCR4,phosphorylated extracellular regulated protein kinase (p-ERK)and total ERK (t-ERK)by Western blot. Results Compared with group S,MWT was significantly decreased and TWL was shortened at T1-5 in group I and group A+I,and the expression of CXCR4and p-ERK in DRGs was significantly up-regulated (P<0.05),and no significant change was found in the expression of t-ERK in group I,no significant change was found in the expression of CXCR4,p-ERK and t-ERK in group A+I,and no significant change was found in the parameters mentioned above in group A+S (P>0.05).Compared with group I,MWT was significantly increased and TWL was prolonged at T1.5,the expression of CXCR4and p-ERK in DRGs was down-regulated (P<0.05),and no significant change was found in the expression of t-ERK in group A+I (P>0.05).Conclusion CXCR4 in DRGs is involved in incisional pain,and the mechanism may be re- lated to activating ERK1/2 signaling pathway in rats.