癌痛外治机制的实验性研究

The Experimental Study of Mechanism in External treatment of Cancer pain

目的以中药止痛贴为例,观察其对骨癌痛大鼠脊髓背角神经节pCaMKⅡ和pCREB表达的影响。方法 108只180～220g雌性Wistar大鼠随机分为3组,分别为空白对照组(Con组,n=24)、假手术组(Sham组,n=24)、骨癌痛模型组(Ca组,n=60),3组分别于手术前2 d、术后每隔4日测定机械痛阈(MWT)和热痛阈(TWL)。于术后7天确认造模成功后,将成功的模型鼠随机分为两组,即模型组(Ca组,n=28)和中药止痛贴组(CM组,n=25)。术后7天、14天和21天各组处死大鼠(n≥8),取大鼠脊髓腰椎L4～6膨大处,用免疫组化方法测定脊髓背角pCaMKⅡ和pCREB的变化。结果脊髓背角神经pCaMKⅡ和pCREB表达:Ca组阳性神经元数目增加,术后7天、术后14、21天与Con组和Sham组比较有统计学差异(P<0.05);CM组于术后14天、术后21天与Con组和Sham组统计学差异逐渐缩小(P>0.05)。结论中药止痛贴对骨癌痛有比较明显的镇痛作用,其对脊髓背角c-fos的影响可能是通过降低脊髓背角CaMKⅡ的表达而产生的,即通过Ca2+-CaM-CaMK-CREB信号转导通路完成的。

Objective The influence of Chinese Medicine Relieve Pain Plaster to the expression of pCaMKⅡand pCREB in the spinal cord dorsal root ganglion of bone pain rats.Methods 108 female Wistar rats（180-220g） were randomly,into blank control group（group Con,n = 24） sham operation group（group Sham,n = 24）,and bone cancer pain model group（group Ca,n = 60）.In the 2 days before operation and every 4 days after operation,the 3 groups were determined of mechanical pain threshold（MWT） and thermal pan threshold（TWL）.On the 7 day postoperatively confirmed after injecting,the success of the model rats were randomly divided into two groups,namely the model group（group Ca,n = 25） and Chinese Traditional Medicine Relieve Pain Plaster group（group CM,n = 18）.After 7 days,14 days and 21 days in each group were sacrificed rats（n≥8）,rat spinal cord lumbar L4-6 modified by immunohistochemical method,the determination of the change of pCaMKⅡand pCREB in spinal dorsal horn.Results Spinal cord dorsal horn neuronal pCaMKⅡand pCREB expression： group Ca number of positive neurons increased,after 7,14,21 days in group Sham compared with statistical difference（P 0.05）;group CM after 14,21 days in group Con and group Sham were compared statistically difference narrowed gradually（P 0.05）.Conclusion Chinese Traditional Medicine Relieve Pain Plaster to the bone cancer pain has obvious analgesic effect,and effects on spinal dorsal horn c-fos effects,possibly by reducing spinal dorsal root ganglion pCaMKⅡexpression and arise,namely through Ca2 ＋-CaM-CaMK-CREB signal transduction pathway completed.