骨癌痛大鼠鞘内注射U0126的抗痛觉过敏作用

摘要

目的 研究鞘内注射(it)U0126对骨癌痛大鼠机械痛敏的影响和对脊髓背角磷酸化cAMP反应元件结合蛋白(pCREB)表达的影响,探讨ERK-CREB信号转导通路在骨癌痛中的作用.方法 ① 40只成年♀SD大鼠分为5组,假模型组Ⅰ和骨癌痛模型组Ⅱ、Ⅲ、Ⅳ、Ⅴ.建模后d 10每只大鼠分别it 10 μg U0126、5%二甲亚砜10 μl和U0126 0.1、1、10 μg(U0126溶于10 μl 5%二甲亚砜中),测机械性缩爪阈值(MWT)和双下肢负重差(WBD);② 25只成年♀SD大鼠分为5组,T1、T2和T3组在制作骨癌痛模型后d 10,it U0126 10 μg后1、6、24 h处死大鼠,M组为模型对照组,it 5%二甲亚砜10 μl后6 h处死大鼠,S组为空白对照组.免疫组化方法测定L4-6术侧脊髓背角pCREB免疫反应阳性神经元数量.结果 鞘内注射U0126 1 μg和10 μg明显逆转了骨癌痛引起的机械痛敏;鞘内注射10 μg U0126明显减少脊髓背角pCREB表达,且效果至少可持续6 h.结论 ERK-CREB通路可能参与骨癌痛.%Aim To investigate the effect of intrathecal ( i. t. ) U0126( MAPK kinase inhibitor ) on the mechanical hyperalgesia and the expression of phosphorylated cAMP response element binding protein( pCREB ) in the dorsal horn of spinal cord following bone cancer pain in rats , trying to evaluate the role played by ERKCREB signal transmission pathway in the mechanism of bone cancer pain. Methods ① 40 adult female SD rats were divided into five groups. Sham group Ⅰ and bone cancer pain ( BCP ) group rats Ⅱ . Ⅲ , Ⅳ , Ⅴ received a bolus of 10 μg U0126. 5％ DMSO 10 μl,U0126 0. 1, 1, 10 μg i. t. respectively on the 10th day after the model was made. Mechanical withdrawal threshold ( MWT ) and weight bearing difference ( WBD ) were measured;②25 adult female SD rats were divided into five groups. On the lOth day after the model was made, BCP rats of group T1 , T2 and T3 were killed at 1, 6. 24 h after i. t. U0126 10 μg respectively. In group M, rats produced bone cancer pain only and were killed at 6h after i. t. 5％ DMSO 10 μl; sham group S was as blank control; L4-6 segments of spinal cord were removed and the expression of pCREB was assessed by immunohistochemical analysis. Results Intrathecal U0126 1μg and 10 μg significantly reversed the mechanical hyperalgesia induced by bone cancer pain. Intrathecal U0126 10 μg significantly attenuated the activation of pCREB in the dorsal horn of spinal cord induced by BCP and the effects lasted for at least 6 h. Conclusion This study shows that ERK-CREB signal cascade is involved in the mechanism of bone cancer pain.