右美托咪定对瑞芬太尼诱发切口痛大鼠痛觉过敏时脊髓p38MAPK表达的影响

Effect of dexmedetomidine on spinal p38MAPK expression during remifentanil-induced postopera-tive hyperalgesia in rats with incisional pain

目的评价右美托咪定对瑞芬太尼诱发切口痛大鼠痛觉过敏时脊髓p38丝裂原活化蛋白激酶（p38MAPK）表达的影响。方法健康雄性SD大鼠48只，6周龄，体重220～250g，采用随机数字表法分为4组（n=12）：对照组（C组）、切口痛组（IP组）、切口痛＋瑞芬太尼组（IP＋R组）和切口痛＋瑞芬太尼＋右美托咪定组（IP＋R＋D组）。切口痛模型制备成功后，IP＋R组尾静脉输注瑞芬太尼1．0μg／kg；IP＋R＋D组尾静脉输注瑞芬太尼1．0μg／kg，同时颈静脉输注右美托咪定10μg／kg；C组和IP组尾静脉和颈静脉输注等容量生理盐水，各组输注时间均为4h。分别于术前24h（T0）和药物输注结束后4、6、24和48h（T1-4）时，测定机械缩足反应阈（MWT）。于T4痛阈测定结束后，采用免疫组化法测定脊髓p38MAPK的表达水平。结果与C组比较，IP组和IP＋R组T1-4时MWT降低，T4时脊髓p38MAPK表达上调（P〈0．05），IP＋R＋D组MWT和脊髓p38MAPK表达差异无统计学意义（P〉0．05）；与IP组比较，P＋R组T1-4时MWT降低，T4时脊髓p38MAPK表达上调，IP＋R＋D组T1-4时MWT升高，T4时脊髓p38MAPK表达下调（P〈0．05）；与IP＋R组比较，IP＋R＋D组T1-4时MWT升高，T4时脊髓p38MAPK表达下调（P〈0．05）。结论右美托咪定减轻瑞芬太尼诱发切口痛大鼠痛觉过敏的机制与下调脊髓p38MAPK的表达有关。

Objective To evaluate the effect of dexmedetomidine on spinal p38 mitogen-activated protein kinase （p38MAPK） expression during remifentanil-induced hyperalgesia in rats with incisional pain. Methods Forty-eight healthy male Sprague-Dawley rats, aged 6 weeks, weighing 220-250 g, were ran- domly divided into 4 groups （n= 12 each） using a random number table： control group （group C） , inci- sion pain group （ group IP） , incision pain ＋ remifentanil group （group IP ＋R） , and incision pain ＋ remifentanil ＋ dexmedetomidine group （group IP＋R＋D）. After successful establishment of the model of in- cisionsal pian, remifentanil 1.0 μg/kg was infused for 4 h via the tail vein in group IP＋R; remifentanil 1.0 μg/kg was infused for 4 h via the tail vein, and dexmedetomidine 10 μg/kg was simultaneously infused for 4 h via the jugular vein in group IP＋R＋D; the equal volume of normal saline was infused for 4 h via the tail and jugular veins in C and IP groups. The mechanical paw withdrawal threshold （MWT） was measured at 24 h before operation （T0） , and at 4, 6, 24 and 48 h after the end of drug infusion （T1-4）. After meas- urement of MWT at T4 , the expression of p38MAPK was determined using immuno-histochemistry. Results Compared with group C, the MWT was significantly decreased at T1-4, and the expression of p38MAPK was up-regulated at T4 in IP and IP＋R groups （P〈0.05） , and no significant change was found in the MWT and expression of p38MAPK in group IP＋R＋D （P〉0.05）. Compared with group IP, the MWT was signifi- cantly decreased at T1-4, and the expression of p38MAPK was up-regulated at T4 in group P＋R, and the MWT was significantly increased at T1-4 , and the expression of p38MAPK was down-regulated at T4 in group IP＋R＋D （P〈0.05）. Compared with group IP＋R, the MWT was significantly increased at T1-4, and the expression of p38MAPK was down-regulated at T4 in group IP＋R＋D （P〈O. 05）. Conclusion The mecha- nism by which dexmedetomidine reduces hyperalgesia induced by remifentanil is related to down-regulation of spinal p38MAPK expression in the rats with incisional pain.