脊髓背角COX-1和COX-2在p38MAPK诱发大鼠切口痛中的作用

目的 评价脊髓背角环氧化酶-1(COX-1)和COX-2在p38丝裂原活化蛋白激酶(p38MAPK)诱发大鼠切口痛中的作用.方法 雄性SD大鼠,体重250～300 g,选择鞘内置管成功的大鼠112只,随机分为4组(n=28):假手术组(S组)、切口痛组(IP组)、二甲基亚砜组(DMSO组)和p38MAPK特异性抑制剂SB203580组(SB203580组).S组鞘内注射0.9%生理盐水20 μl后,吸入异氟烷(呼气末浓度1.4%)min,不做手术;IP组术前10 min鞘内注射0.9%生理盐水20 μl;DMSO组和SB203580组术前10 min分别鞘内注射2%DMSO(SB203580的溶媒)10 μl和SB203580 30 μg(10 μl),然后用0.9%生理盐水10 μl冲洗导管.于鞘内置管后5 d,制备大鼠左后足切口痛模型.各组于术前1 h、术后2、3、6 h和1、2、3、5 d时,测定机械缩足反射阈值(MWT)和热刺激缩足反射潜伏期(TWL).各组于术后2、3、6 h和1、2、3、5 d痛阈测定结束后各处死4只大鼠,采用Western blotting法测定脊髓背角COX-1和COX-2的表达水平.结果 与S组比较,IP组和DMSO组术后2 h～2 d时MWT降低,术后2 h～3 d时TWL缩短,IP组、DMSO组和SB203580组术后3 h～3 d脊髓背角COX-1表达上调(P<0.05);与IP组和DMSO组比较,SB203580组术后2 h～1 d时MWT升高,术后2 h～2 d时TWL延长,术后6 h～2 d脊髓背角COX-1表达下调(P<0.05);4组术后各时点脊髓背角COX-2表达差异无统计学意义(P>0.05).结论 p38MAPK诱发大鼠切口痛与脊髓背角COX-1有关,与COX-2无关.

Role of COX-1 and COX-2 In spinal dorsal horn In Incisional pain Induced by p38MAPK in rats

Objective To evaluate the role of COX-1 and COX-2 in the spinal dorsal horn in incisional pain induced by p38MAPK in rats.Methods Male SD rats weighing 250-300 g were used in this study.The animals were anesthetized with intraperitoneal pentobarbital 40 mg/kg.A PE-10 catheter was inserted into the subarachnoid space with the tip positioned at the lumbar enlargement according to the method described by Yaksh et al.One hundred and twelve SD rats in which IT catheter was successfully placed without any complication were randomly divided into 4 groups with 28 animals in each group: group Ⅰ sham operation (S) ; group Ⅱ incisional pain (IP) : group Ⅲ IT SB203580 + IP and group Ⅳ IT DMSO (the solvent) + IP.An 1 cm long incision was made in the plantar surface according to the method described by Brennan et al.The animals were killed at 2,3,6 h,1,2,3,5 d after operation ( n = 4,at each time point).The L4-5 segment of the spinal cord was removed for determiuation of expression of COX-1 and COX-2 in the spinal dorsal horn (by Western blot).Results Incisional pain significantly increased the expression of COX-1 protein in the spinal dorsal horn at 2,3,6 h and 1,2,3 d after incision in group Ⅱ and Ⅳ as compared with sham operation group.IT SB203580 significantly inhibited the incisional pain induced increase in COX-1 in the spinal dorsal horn in group Ⅲ as compared with group Ⅱ and Ⅳ.There was no significant difference in the expression of COX-2 in the spinal dorsal horn among the 4 groups.Conclusion COX-1 but not COX-2 in the spinal dorsal horn is involved in incisional pain induced by p38MARK.