μ受体介导靶向毁损脑干下行易化神经元对骨癌痛大鼠的镇痛效应  

Analgesic effects of the selective blocking of descending facilitation targeting it opioid receptor positive neurons in a rat model of bone cancer pain

作　　者：曹菲[1] 陈莎莎 刘希江[1] 肖兴鹏[1] 杨少兵[1] 许爱军[1] 高峰[1] 杨辉[1] 田学愎[1] 梅伟[1] 田玉科[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉科,武汉市430030

出　　处：《中华麻醉学杂志》2009年第11期992-996,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30672027、30901396）;高等学校博士学科点专项科研基金资助项目（20060487048）

摘　　要：目的探讨μ受体介导靶向毁损脑干下行易化神经元对骨癌痛大鼠的镇痛效应。方法成年雌性Wistar大鼠48只，体重180—200g，随机分为6组，对照组（n=3）：不给予任何处理；骨癌痛组（n=9）：于右下肢胫骨中部骨髓腔内注射Walker 256乳腺癌细胞10μl制备骨癌痛模型；PBS组（n=9）：乳腺癌细胞接种前28d时延髓头端腹内侧（RVM）区单次微注射PBS；皮啡肽组（n＝9）：乳腺癌细胞接种前28d时RVM区单次微注射皮啡肽；皂角索组（n＝9）：乳腺癌细胞接种前28d时RVM区单次微注射皂角素；皮啡肽-皂角素耦联体组（n=9）：乳腺癌细胞接种前28d时RVM区单次微注射皮啡肽-皂角素耦联体。于乳腺癌细胞接种前1d、乳腺癌细胞接种后3、5、7、9、11、14、16、18、20d时测定机械痛阈。c组于乳腺癌细胞接种后20d时，其余各组于乳腺癌细胞接种后7、14和20d时，各处死3只大鼠，测定脊髓背角Fos蛋白表达水平。结果与对照组比较，骨癌痛组、皮啡肽组和皂角素组接种侧机械痛阈乳腺癌细胞接种后7～20d时降低，接种对侧机械痛阈乳腺癌细胞接种后9～20d时降低，接种侧和接种对侧脊髓背角Fos蛋白表达上调，皮啡肽-皂角素组接种侧机械痛阈乳腺癌细胞接种后7～14d时降低，接种对侧机械痛阈乳腺癌细胞接种后9～14d时降低，皮啡肽组一皂角素组乳腺癌细胞接种后7d时接种侧和接种对侧脊髓背角Fos蛋白表达上调（P〈0．05）；与骨癌痛组比较，皮啡肽组和皂角素组接种侧和接种对侧各时点机械痛阈和脊髓背角Fos蛋白表达差异无统计学意义（P〉0．05），皮啡肽-皂角素组接种侧机械痛阈乳腺癌细胞接种后11～20d时升高，接种对侧机械痛阂乳腺癌细胞接种后4～20d时升高，乳腺癌细胞接种后14、20d时接种侧和接种对侧脊髓背角Fos蛋白表达下调（P〈0．05）。结论 μ受体介导靶向毁损脑干下Objective To investigate analgesic effects of the selective blocking of descending facilitation targeting μ opioid receptor positive neurons in the rostral ventromedial medulla （RVM） in a rat model of bone cancer pain. Methods Forty-eight adult female Wistar rats weighing 180-200 g were randomly divided into 6 groups ： group Ⅰ control （ n = 3 ） ; group Ⅱ bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells （ n = 9） ; group Ⅲ- Ⅳ received a single intra-RVM micro-injection of PBS （group Ⅲ ）, dermorphin （group Ⅳ ）, saporin （group Ⅴ ） and dermorphin-saporin （group Ⅵ ） respectively at 28 days before intra-tibia inoculation （n = 9 each）. Starting from 3 to 20 days after intra-tibia inoculation, mechanical allodynia was assessed and recorded. The animals were sacrificed on 7, 14 and 20 days after intra-tibia inoculation, after repetitive non-noxious tactile stimulation of the hindpaw. The total number of Fos-positive neurons in the spinal dorsal horn was measured as a marker indicative of central sensitization. Results The animals developed nociceptive hypersensitivity after intra-tibia cancer cell inoculation in group Ⅱ -Ⅵ . Nociceptive hypersensitivity was significantly decreased during 4-7 days after the onset of nociception in group Ⅵ （dermorphinsaporin）. The number of Fos positive neurons in bilateral spinal dorsal horn was significantly increased by intratibia inoculation of cancer cells in group Ⅱ - Ⅵ as compared with control group and was significantly lower at day 14 and 20 after inoculation in group Ⅵ （dermorphin-saporin） than in group Ⅱ -Ⅴ . Conclusion Selective blocking of descending facilitation targeting μ opioid receptor positive neurons in RVM can effectively reduce nociceptive hypersensitivity induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells.

关 键 词：受体 阿片样 疼痛 镇痛 

分 类 号：R738.1[医药卫生—肿瘤]