摘要目的 评价脊髓趋化因子CC亚族受体5(CCR5)在瑞芬太尼诱发切口痛大鼠痛觉过敏中的作用.方法 取鞘内置管和尾静脉置管成功的雄性SD大鼠32只,体重240～260 g,2～3月龄,采用随机数字表法分为4组(n=8):对照组(C组)、CCR5拮抗剂maraviroc组(M组)、瑞芬太尼+切口痛组(R+I组)和maraviroc+瑞芬太尼+切口痛组(M+R+I组).C组鞘内注射PBS 10μl,尾静脉输注生理盐水1 μg·kg-1·min-160 min;M组鞘内注射maraviroc 100 pmol(溶于10μl PBS中),尾静脉输注生理盐水1 μg·kg-1·min-160 min;R+I组鞘内注射PBS 10μl,然后建立切口痛模型,同时尾静脉输注瑞芬太尼1 μg·kg-1·min-160 min;M+R+I组鞘内注射maraviroc 100 pmol(溶于10μl PBS中),然后建立切口痛模型,同时尾静脉输注瑞芬太尼lμg·kg-1·min-160 min.于输注瑞芬太尼或生理盐水前24 h(T0)、停止输注瑞芬太尼或生理盐水后2、6、24和48 h(T1-4)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,取脊髓L4-6节段,采用Western blot法测定胶质纤维酸性蛋白(GFAP)和离子钙接头分子1(Iba-1)的表达水平.结果 与C组比较,R+I组和M+R+I组T1-4时MWT降低,TWL缩短,脊髓GFAP和Iba-1的表达上调(P＜0.05),M组上述各指标差异无统计学意义(P＞0.05).与R+I组比较,M+R+I组T1-4时MWT升高,TWL延长,脊髓GFAP和Iba-1的表达下调(P＜0.05).结论 脊髓CCR5参与了瑞芬太尼诱发切口痛大鼠痛觉过敏,其机制可能与激活星形胶质细胞和小胶质细胞有关.

abstractsObjective To evaluate the role of spinal C-C motif chemokine receptor 5 (CCRS) in remifentanil-induced hyperalgesia in rats with incisional pain.Methods Thirty-two male Sprague-Dawley rats,weighing 240-260 g,aged 2-3 months,in which intrathecal and caudal catheters were successfully implanted,were divided into 4 groups (n =8 each) using a random number table:control group (group C),CCR5 antagonist maraviroc group (group M),remifentanil plus incisional pain group (group R + I) and maraviroc plus remifentanil plus incisional pain group (group M + R + I).Phosphate buffer solution (PBS) 10 μl was intrathecally injected and normal saline was infused for 60 rnin at 1 μg · kg-1 · min-1 via the caudal vein in group C.Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected and normal saline was infused for 60 min at 1 μg · kg-1 · min-1 via the caudal vein in group M.PBS 10 μl was intrathecally injected,then the model of incisional pain was established,and remifentanil 1 μg · kg-1 · min-1 was infused for 60 min via the caudal vein in group R+I.Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected,then the model of incisional pain was established,and remifentanil 1 μg · kg-1 · min-1 was infused for 60 min via the caudal vein in group M+R+I.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion of remifentanil or normal saline (T0) and 2,6,24 and 48 h after stopping infusion (T1-4).The rats were sacrificed after the last measurement of pain threshold,and L4-6 segments of the spinal cord were removed for determination of the expression of glial fibrillary acidic protein (GFAP) and ionized calciumbinding adapter molecule-1 (Iba-1) by Western blot.Results Compared with group C,the MWT was significantly decreased and TWL was shortened at T1-4,and the expression of GFAP and Iba-1 in the spinal cord was up-regulated in R+I and M+R+I groups (P＜0.05),and no significant change was found in the parameters mentioned above in group M (P＞0.05).Compared with group R+I,the MWT was significantly increased and TWL was prolonged at T1-4,and the expression of GFAP and Iba-1 in the spinal cord was down-regulated in group M+R+I (P＜0.05).Conclusion Spinal CCR5 is involved in remifentanil-induced hyperalgesia in the rats with incisional pain,and the mechanism may be related to activating astrocytes and microglias.