Zhang Fei-E, Cao Jun-Li, Zhang Li-Cai, Zeng Yin-Ming
Jiangsu Institute of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou 221002, China.
Sheng Li Xue Bao. 2005 Oct 25;57(5):545-51.
The present study aimed to investigate the role of spinal p38 mitogen-activated protein kinase (p38 MAPK) activation in chronic constriction injury (CCI) of the sciatic nerve induced neuropathic pain. CCI model was produced by loosely ligating the left sciatic nerve proximal to the sciatica's trifurcation with 4-0 silk thread in male Sprague-Dawley rat. SB203580, a specific inhibitor of the p38 MAPK, was intrathecally administered on day 5 post-CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and the paw withdrawal threshold (PWT) to von Frey filaments respectively. The protein levels of the phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated cAMP response element binding protein (pCREB) were assessed by Western blot analysis. The results showed that CCI significantly increased the expressions of cytosolic and nuclear p-p38 MAPK in the spinal cord. Intrathecal administration of SB203580 dose-dependently reversed the established mechanical allodynia and thermal hyperalgesia induced by CCI. Correlated with behavior results, SB203580 dose-dependently inhibited the CCI-induced increase of the expressions of cytosolic and nuclear p-p38 MAPK and nuclear pCREB in the spinal cord. Taken together, these findings suggest that the activation of p38 MAPK pathway contributes to the development of neuropathic pain induced by CCI, and that the function of p-p38 MAPK may partly be accomplished via the CREB-dependent gene expression.
本研究旨在探讨脊髓p38丝裂原活化蛋白激酶（p38 MAPK）激活在坐骨神经慢性压迫损伤（CCI）诱导的神经性疼痛中的作用。在雄性Sprague-Dawley大鼠中，通过用4-0丝线在坐骨神经三叉分支近端松散结扎左侧坐骨神经来建立CCI模型。在CCI术后第5天鞘内注射p38 MAPK的特异性抑制剂SB203580。分别用对辐射热的爪退缩潜伏期（PWL）和对von Frey细丝的爪退缩阈值（PWT）评估热和机械性伤害性感受阈值。通过蛋白质印迹分析评估磷酸化p38 MAPK（p-p38 MAPK）和磷酸化cAMP反应元件结合蛋白（pCREB）的蛋白水平。结果显示，CCI显著增加了脊髓中胞质和核p-p38 MAPK的表达。鞘内注射SB203580剂量依赖性地逆转了由CCI诱导的已确立的机械性异常性疼痛和热痛觉过敏。与行为结果相关，SB203580剂量依赖性地抑制了CCI诱导的脊髓中胞质和核p-p38 MAPK以及核pCREB表达的增加。综上所述，这些发现表明p38 MAPK通路的激活有助于CCI诱导的神经性疼痛的发展，并且p-p38 MAPK的功能可能部分通过CREB依赖性基因表达来实现。
