目的探讨鞘内注射雷帕霉素对小鼠神经痫理性痛行为的影响。方法选择鞘内置管成功尢运动障碍及严承体重减轻的成年雄性C57/B16小鼠48只,随机分为两组:假手术组(sham组,n=24)和慢性坐骨神经损伤模犁组(CCl组,n=24)。建讥模型后将各组随机分为3组,组一不做任何处理,组二在术后1~6d鞘内注射雷帕霉素1μg/5μl,组三鞘内给予溶媒20%DMSO 5μl(sham,sham+R,sham+V,CCI,CCI+R,CCI+V,n=8)。在手术前1d,于术后1d,3d,5d,7d,10d,14d,17d,21d,28d检测小鼠双侧足底机械缩足阈值(Mechanical Withdraw Threshold,WMT)和热辐射缩足潜伏期(Thermal Withdraw Latency,TWL);结果与Sham组相比,CCI组小鼠手术侧足底MWT和TWL均明显降低[第7天,MWT:(1.02±0.12)g,(0.42±0.12)g,F:51.01,P〈0.05;TWL:(7.03±0.71)s,(3.26±0.66)s,F=38.27,P〈0.05]。而CCI后1—6d鞘内注射宙帕霉素1μg/5μl。,使小鼠的MWT明显升高[第7天,(0.42±0.18)g,(0.86±0.25)g,F=6.56,P〈0.05],并U至少持续至术后10d。与之相对的,雷帕霉素对CCI小鼠的热痛觉过敏也有缓解趋势,但筹异无统计学意义。sham组和对侧足底痛行为未见明显改变(P〉0.05)。结论鞘内注射雷帕霉素可以明显缓解CCI小鼠的机械痛觉异常,但埘热痛觉过敏无显著作用。
Objective To investigate the effects of continuously intrathecal injection rapamyein on neuropathie pain behaviors in mice. Methods 48 male adult C57/BL6 mice received intrathecal catheter implantation successfhlly ami without motor dysfunction anti serious weight loss,were choosed and randomly divided into shamoperation group (sham, n = 24) and chronic constriction injury model group (CCI, n = 24 ). After operation, each group randomly divided into 3 group again. Group Ⅰ did nothing,group Ⅱ intrathecally injected rapamycin 1μg/5μl on day 1 to 6 after operation,group HI intratheeally injected 20% DMSO 5μl on the same time ( sham,CCl,sham + R,sham + V,CCI + R,CCI + V, n = 8). Bilateral mechanical paw withdrawal threshold(WMT) and thermal paw withdrawal latency(TWL) were tested on day I before CCI and day 1,3,5,7,10,14,17,21,28 after operation. Results Compared with sham group,both WMT and TWL (7d,MWT:(1.02 ±0.12)g vs (0.42±0.12)g, F= 51.01, P 〈 0.05 ; TWL : ( 7.03 ± 0.71 ) s vs ( 3.26 ± 0.66 ) s, F = 38.27, P 〈 0.05 ) were significantly decreased after CCI on the ipsilateral side. When intrathecally injected Rapamyein 1 μg/5μl on day 1 - 6 after CCI, the mechanical allodynia relieved obviously(7d, MWT: (0.42 ±0. 18) g vs (0.86 ±0.25)g, F=6.56, P〈0.05 ) ,and at least continued to 10 d. On the contrary,the effects of rapainycin on thermal hyperalgesia just showed a trend of inhibition,there was no statistic meaning. In addition,the sham group and contralateral pain behaviors did not change (P〉 0.05). Conclusion Rapamycin can relieve the neuropathie pain behaviors in mice after CCI,mainly the mechanical allodynia,but not thermal hyperalgesia.