鞘内注射雷帕霉素对小鼠神经病理性痛行为的影响

目的 探讨鞘内注射雷帕霉素对小鼠神经病理性痛行为的影响.方法 选择鞘内置管成功无运动障碍及严重体重减轻的成年雄性C57/BL6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型组(CCI组,n=24).建立模型后将各组随机分为3组,组-不做任何处理,组二在术后1～6 d鞘内注射雷帕霉素1μg/5μl,组三鞘内给予溶媒20％ DMS0 5μl(sham,sham+R,sham+V,CCI,CCI+R,CCI+V,n=8).在手术前1d,手术后1d,3d,5d,7d,10d,14 d,17d,21d,28 d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鞘内注射雷帕霉素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],并且至少持续至术后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,但差异无统计学意义.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,但对热痛觉过敏无显著作用.

Effects of intrathecal injection rapamycin on neuropathic pain behaviors in mice

Objective To investigate the effects of continuously intrathecal injection rapamycin on neuro pathic pain behaviors in mice.Methods 48 male adult C57/BL6 mice received intrathecal catheter implantation successfully and without motor dysfunction and 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 1 μg/5μlon day 1 to 6 after operation,group Ⅲ intrathecally injected 20％ DMSO 5μl on the same time ( sham,CCI,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 1 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 Rapamycin 1 μg/5 μl on day 1 ～6 after CCI,the mechanical allodynia relieved obviously ( 7 d,M WT:( 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 rapamycin 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 neuropathic pain behaviors in mice after CCI,mainly the mechanical allodynia,but not thermal hyperalgesia.