瑞芬太尼诱发的大鼠焦虑样行为与阿片类药物痛觉敏化的关系  

Relationship between remifentanil-induced anxiety-like behavior and opioid-induced hyperalgesia

作　　者：贾辰飞[1] 杨笑萱 陈丽娇[1] 薛庆生[1] 于布为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,上海200025

出　　处：《上海医学》2014年第12期1023-1027,I0001,共6页Shanghai Medical Journal

基　　金：上海交通大学医学院科技基金资助项目(13XJ10009)

摘　　要：目的通过研究大鼠静脉输注瑞芬太尼后情绪性反应网络的作用，探索阿片类药物痛觉敏化的机制。方法成年健康Sprague-Dawley大鼠60只，体重290～310g，在七氟烷吸入麻醉下予瑞芬太尼（瑞芬太尼组，30只）或0．9％氯化钠溶液（对照组，30只）持续静脉内输注2h建模，分别在术后2、6、24h采用行为学和形态学的方法研究瑞芬太尼引起的大鼠行为和脑内情绪反应相关核团的变化。结果两组大鼠术后2h的机械性痛阈缩足阈值均显著低于同组基础值（P值均〈0．05），两组大鼠术后2h的热痛阈缩足潜伏期与同组基础值的差异均无统计学意义（P值均〉0．05），两组间同时间点缩足阈值和缩足潜伏期的差异均无统计学意义（P值均〉0．05）。两组大鼠在术后2、6、24h旷场实验5min内的行走距离的差异均无统计学意义（P值均〉0．05）。瑞芬太尼组大鼠在术后2h的高架十字迷宫实验开放臂进入次数和停留时间均显著少于同组术后6、24h和对照组各时间点（P值均〈0．01），闭合臂停留时间显著长于同组术后6、24h和对照组各时间点（P值均〈0．01）；在术后6h的开放臂进人次数显著少于对照组同时间点（P〈0．01）。组内不同时间点间和组间同时间点闭合臂进入次数的差异均无统计学意义（P值均〉0．05）。瑞芬太尼组术后2、6h的前扣带回c-Fos和NeuN共染色神经元计数分别显著高于对照组同时间点（P值分别〈0．01、0．05），且c-Fos仅在前扣带回的外颗粒细胞层和外椎体细胞层表达明显增加。结论瑞芬太尼诱发痛觉敏化的发生可能不是由伤害感受的阈值降低所致，而是通过诱发短期焦虑样行为，改变了疼痛体验的中枢整合过程。Objective To investigate the remifentanil induced anxiety-like behavior and the mechanism of hyperalgesia induced by opioids. Methods Sixty healthy adult Sprague-Dawley rats weighing 290- 310 g were randomly divided into remifentanil group and control group （n = 30）. After 2 h infusion of remifentanil （remifentanil group） or normal saline （control group） under sevoflurane anesthesia, the changes of c-Fos expression in anterior cingulate cortex （ACC） were investigated when anxiety-like behavior was measured by elevated plus-maze （EPM） test and open field test. Paw withdrawal threshold （PWT） and paw withdrawal latency （PWL） were measured 24 h before anesthesia and 2 h, 6 h, and 24 h after operation. Results PWT was significantly decreased at 2 h after operation compared with the baselines （both P〈0.05）, while PWL at 2 h after operation was not significantly different from the baselines in both groups （both P〉0. 05）. There were no significant differences in terms of PWT and PWL between groups （all P〉0.05）, nitheer were the walking distances of open field test at 2 h, 6 h, and 24 h after operation （all P〉0.05）. The frequency of open arm＇s entries and the time spent in open arm in the EPM test at 2 h after infusion of remifentanil were greatly reduced as compared with those in the remifentanil group at 6 h and 24 h after infusion of remifentanil and those in the control group at each time point （all P〈0. 01）. The time spent in close arm in the EPM test at 2 h after infusion of remifentanil was significantly more than those in theremifentanil group at 6 h and 24 h after infusion of remifentanil and those in the control group at each time point （all P〈0.01）. The frequency of open arm＇s entries at 6 h after infusion of remifentanil was significantly less than that in the control group （P〈0.01）. The c-Fos/neuronal nuclei （NeuN）-positive cells in the layer Ⅱ/Ⅲ of anterior cingulated cortex in the remifentanil group were significantly more tha

关 键 词：SPRAGUE-DAWLEY大鼠 前扣带回 痛觉敏化 焦虑样行为 

分 类 号：R614[医药卫生—麻醉学]