国际麻醉学与复苏杂志   2014, Issue (4): 10-10
    
小胶质细胞参与尼古丁戒断切口痛大鼠术后痛觉过敏的研究
刘献文, 张宗旺1()
1.徐州医学院麻醉学院
Spinal microglia contributes to postoperative hyperalgesia in incisional rats with nicotine abstinence
 全文:
摘要:

目的 探讨脊髓小胶质细胞在尼古丁戒断切口痛大鼠术后痛觉过敏中的作用。 方法 SD大鼠42只采用随机数字表法随机分为3组。单纯切口痛组(IP组,18只):依处死时间再分为3亚组(每组6只),均做切口痛模型;尼古丁戒断切口痛组(N+IP组,18只):依处死时间再分为3亚组(每组6只),皮下注射尼古丁连续7 d后做切口痛模型;米诺环素组(M组,6只):同N+IP组,做切口痛模型前1 h腹腔内注射米诺环素100 mg/kg。所有大鼠分别于术后第1、2、3、5、7天对大鼠术侧行机械刺激缩足阈值(mechanical withdrawal threshold, MWT)和热刺激缩足潜伏期(thermal withdrawal latency, TWL)测定。IP组和N+IP组大鼠在术后第1、3、7天痛行为学测试后处死。取脊髓L4~6段,免疫组织化学法测定Ca2+接头蛋白(ionized calcium binding adapter molecule-1, IBA-1)阳性细胞的表达。 结果 与IP组比较,N+IP组大鼠在术后1 d~7 d MWT和TWL均显著降低(P<0.01);与N+IP组比较,M组大鼠在术后第1天 MWT[(28.1±1.7) g vs (22.3±2.4) g]和TWL[(7.5±1.3) s vs (5.2±1.2) s ]明显升高(P<0.01),而第2天~第7天无变化(P>0.05)。组内比较,IP组大鼠脊髓背角IBA-1阳性细胞术后第3天比术后第1天和第7天明显增多(P<0.01)。与IP组比较,在术后第1、3、7天N+IP组大鼠IBA-1阳性细胞明显增多(P<0.01)。 结论 尼古丁暴露引起大鼠脊髓背角小胶质细胞活化,小胶质细胞活化参与了尼古丁戒断切口痛大鼠术后痛觉过敏。

关键词: 尼古丁;戒断;切口痛;小胶质细胞;米诺环素
Abstract:

Obective To explore whether spinal microglia contributes to postoperative hyperalgesia in incisional rats with nicotine abstinence. Methods Forty-two SD rats were randomized into one of the 3 groups of rats. IP Group(n=18) which was divided into 3 sub-groups according to the executed time, six rats in each group. The rats underwent incisional pain model. N+IP group(n=18) which was divided into 3 sub-groups according to the executed time, six rats in each group. The rats underwent incisional pain model after subcutaneous injection of nicotine for 7 d. M group(n=6): besides all the procedures conducted in the N+IP group, the rats were given intraperitoneal injections of minocycline 100 mg/kg one hour before surgery. For all rats, mechanical withdrawal threshold (MWT) and thermal withdrawal latency(TWL) were determined on the 1st, 2nd, 3rd, 5th and 7th day after surgery. The rats in IP group and N+IP group were executed after NWT and TWL tests on the 1st, 3rd and 7th day after surgery, and then the lumbar enlargement of spinal cord L4?蛳6 were collected. Ionized calcium binding adapter molecule?蛳1(IBA?蛳1) positive cells were determined by immune?蛳histochemical method. Results Compared with IP group, MWT and TWL in N+IP group were significantly lower on the 1st, 2nd, 3rd, 5th and 7th day after surgery(P<0.01). Compared with N+IP group, MWT[(28.1±1.4) g vs (22.3±2.4) g] and TWL[(7.5±1.3) s vs (5.2±1.2) s] in M group were significantly higher on the first day after surgery(P<0.01), whereas no differences were found on the 2nd, 3rd, 5th and 7th day after surgery(P>0.05). In IP group, the number of IBA-1-positive cells in spinal dorsal was significantly higher on the 3rd day than those on 1st and 7th day after surgery (P<0.01). Compared with IP group, the number of IBA-l-positive cells in N+IP group was higher on the 1st, 3rd and 7th day after surgery(P<0.01). Conclusions Nicotine exposure could activate spinal microglia which might contribute to postoperative hyperalgesia in incisional rats with nicotine abstinence.

Key words: Nicotine; Withdrawal; Incision Pain; Microglia; Minocycline