改良尼古丁依赖-戒断大鼠模型的建立与疼痛敏感性观察

Establishment of modified nicotine dependence-withdrawal rat model and observation of pain sensitivity

目的通过间断皮下注射尼古丁制作改良尼古丁依赖碱断大鼠模型，观察尼古丁戒断后大鼠机械刺激缩足阈值（mechanical withdrawal threshold，MwT）和热刺激缩足潜伏期（thermal withdrawal latency，TWL）的变化。方法sD大鼠30只，采用随机数字表法随机分成5组，每组6只：正常对照组（Control组）、生理盐水组（NS组）、尼古丁3mg·kg^-1·d^-1组（NT3组）、尼古丁9mg·kg^-1·d^-1组（NT9组）和尼古丁18mg·kg^-1·d^-1组（NT18组），分别不注射，皮下注射生理盐水、尼古丁1mg／kg、3ms／ks和6mg／kg，3次／d，连续7d。末次注射后60min皮下注射美加明1mg／kg。观察大鼠注射尼古丁期间和戒断后体重变化、存活情况和尼古丁戒断评分。另外选取Control组、NS组和NT9组各6只大鼠，测定右下肢足底MWT和TWL。结果与NT3组比较，注射尼古丁后第7天，NT9组和NT18组大鼠体重增加缓慢[（3．8±1．3）、（2．0±0.3）gVS（7．2±1．0）g]（P〈0．05），戒断后第1天和第2天大鼠体重增加迅速（P〈0．01）。NT9组和NT18组大鼠美加明激发后出现更多的戒断症状（P〈0．01），NT18组大鼠死亡率为17％。与Control组比较，NT9组大鼠在尼古丁戒断后MWT与TWL明显降低（P〈0．01）。结论间断皮下注射尼古丁9mg·kg^-1·d^-1 7d可以成功制作改良尼古丁依赖碱断大鼠模型，尼古丁戒断后大鼠疼痛敏感性增高。

Objective To establish a modified rat model of nicotine dependence-withdrawal syndrome by subcutaneous injection of nicotine, and observe mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） after nicotine withdrawal. Methods Thirty SD rats, were randomly divided into 5 groups with 6 rats per group, including control group, normal saline group （NS group）, nicotine 3 mg＇kg-~＇d1 group （NT3 group）, nicotine 9mg·kg^-1·d^-1 group （NT9 group） and nicotine 18 mg·kg^-1·d^-1 group （NT18 group）, received no injection, subcutaneous injection of normal saline, nicotine 1, 3 mg/kg and 6 mg/kg respectively three times a day for seven days. At 60 min after the last injection of nicotine, subcutaneous injection of mecamylamine 1 mg/kg was given for each rat. Weight changes of rat during injections of nicotine and after nicotine withdrawal, survival rate and its withdrawal symptoms score were recorded. In addition, control group, NS group and NT9 group with 6 rats in each group were selected for the determination of MWT and TWL in the right hind paw during nicotine withdrawal. Results Compared with NT3 group, on the seventh day after injection of nicotine, weight gain of the rats was significantly slow in NT9 group and NT18 group [ （3.8±1.3）, （2.0± 0.3） g vs （7.2±1.0） g ]（P〈0.05）. On the first and second withdrawal days, weight gain of the rats was significantly rapid in NT9 group and NT18 group （P〈0.01）. Compared with NT3 group, the rats in NT9 group and NT18 group had significant more withdrawal symptoms after meeamylamine injection （P〈0.01）. The incidence of mortality in NT18 group was 17%. MWT and TWL decreased significantly after nicotine withdrawal in NT9 group than control group （P〈0.01）. Conclusions A modified rat model of nicotine dependence-withdrawal syndrome can be successfully established by discontinuous subcutaneous injection of nicotine 9 mg·kg^-1·d^-1 for seven days. The pain sensitivity increases in rats with nicotine withdrawal.