p38MAPK信号转导通路在大鼠骨癌痛中的作用

目的 探讨p38丝裂原活化蛋白激酶(p38MAPK)信号转导通路在大鼠骨癌痛中的作用.方法 雌性sD大鼠56只,体重150～170 g,随机分为4组(n=14):生理盐水对照组(NS组)、骨癌痛组(BC组)、二甲基亚砜组(DMSO组)和p38MAPK抑制剂组(SB203580组).骨髓腔内注射Walker256细胞悬液制备大鼠骨癌痛模型,注射后10 d,DMSO组和SB203580组分别鞘内注射5%二甲基亚砜和SB203580(10 μg)10 μl.各组随机取8只大鼠,于注射Walker256细胞悬液前、注射后1、3、5、7、10 d,鞘内给药后1、3、6、12、24 h时采用von Frey纤维丝测定术侧后爪机械缩足反射阈值(MWT);各组余6只大鼠鞘内给药后6 h时取L_(4,5)脊髓,采用免疫组化法检测脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(pCREB)的表达水平.结果 骨髓腔内注射Walker256细胞悬液后7 d大鼠术侧后爪MWT开始降低,鞘内注射SB203580提高了MWT;骨髓腔内注射Walker256细胞悬液后脊髓背角pCREB表达上调,鞘内注射SB203580后脊髓背角pCREB表达下调.结论 鞘内注射SB203580可通过抑制脊髓背角pCREB的表达减轻骨癌痛;p38MAPK信号转导通路在骨癌痛中起重要作用.

Role of p38 mitogen-activated protein kinase In bone cancer pain in rats

Objective To investigate the role of p38 mitogen-activated protein kinase(p38MAPK) in bone cancer pain in rats.Methods Fifty-six female SD rats weighing 150-170 g were randomly divided into 4 groups (n= 14 each): group ⅠNS operation; group Ⅱ bone cancer pain; group Ⅲ DMSO and group Ⅳ SB203580. Bone cancer pain was induced by injecting Walker256 mammary gland cancer cell suspension (107 cells/ml) 5 μl into the bone marrow of left tibia in group Ⅱ,Ⅲ and Ⅳ.5% DMSO 10 μl and SB203580 10 μg in 10 μl were injected IT in group Ⅲ and Ⅳ respectively at 10 days after bone cancer pain model was established. Paw withdrawal threshold to von Frey filament stimulation was measured before and at 1,3,5,7,10 d after bone cancer pain model was established and at 1,3,6, 12,24 h after IT DMSO or SB203580 injection. Six animals in each group were killed at 6 h after IT DMSO and SB203580 injection. The L_(4,5) lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal born by immuno-histochemistry. Results The rats developed hyperalgesia at 7 d after bone cancer pain had been induced. IT SB203580 significantly increased mechanical pain threshold. The number of pCREB positive neurons in the dorsal horn of L_(4,5) segment of the spinal cord was significantly increased by bone cancer pain. IT SB203580 significantly attenuated the increase in pCREB expression induced by bone cancer pain. Conclusion Intrathecal SB203580 can relieve the hyperalgesia induced by bone cancer pain and inhibit CREB phosphorylation in the spinal dorsal horn. p38MAPK signal pathway plays an important role in bone cancer pain.