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脊髓p38丝裂原活化蛋白激酶激活参与坐骨神经压迫性损伤所致神经病理性痛

张飞娥, 曹君利, 张励才, 曾因明

江苏省麻醉医学研究所，江苏省麻醉学重点实验室.江苏,徐州 221002

摘要

该研究旨在观察脊髓p38 丝裂原活化蛋白激酶(p38 mitogen--activated protein kinase, p38 MAPK)在坐骨神经压迫性损伤所致神经病理性痛中的作用。雄性Sprague--Dawley大鼠鞘内置管后，4--0丝线松结扎左侧坐骨神经制作慢性压迫性损伤 (chronic constriction injury, CCI) 模型。CCI 后d5，鞘内注射不同剂量的p38 MAPK特异性抑制剂SB203580，并在给药前及给药后不同时间点，分别用von Frey机械痛敏监测仪和热辐射刺激仪监测大鼠损伤侧后爪机械和热刺激反应阈值，用免疫印迹技术(Western blot)观察给药前后脊髓磷酸化p38 MAPK (p--p38 MAPK)和磷酸化环磷酸腺苷反应元件结合蛋白(phosphorylated cAMP response element binding protein, pCREB)表达变化。结果发现：坐骨神经压迫性损伤引起脊髓p--p38 MAPK蛋白表达明显增加；鞘内注射SB203580能剂量依赖性逆转CCI引起的机械性痛觉异常和热痛觉过敏及脊髓水平p--p38 MAPK表达的增加，也明显抑制CCI引起的脊髓pCREB表达的增加。结果提示，脊髓水平p38 MAPK激活参与坐骨神经压迫性损伤所致神经病理性痛的发展，其作用可能通过pCREB介导。

关键词： p38丝裂原活化蛋白激酶; cAMP反应元件结合蛋白; 神经病理性痛; 脊髓

Activation of p38 mitogen--activated protein kinase in spinal cord contributes to chronic constriction injury--induced neuropathic pain

Zhang Feie, Cao Junli, Zhang Licai, Zeng Yinming

Jiangsu Institute of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology.Xuzhou 221002,Jiangsu

Abstract

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.

Key words: p38 mitogen-activated protein kinase;cAMP response element binding protein;neuropathic pain;Spinal cord

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引用本文：

张飞娥, 曹君利, 张励才, 曾因明. 脊髓p38丝裂原活化蛋白激酶激活参与坐骨神经压迫性损伤所致神经病理性痛 [J]. 生理学报 2005; 57 (5): .

Zhang Feie, Cao Junli, Zhang Licai, Zeng Yinming. Activation of p38 mitogen--activated protein kinase in spinal cord contributes to chronic constriction injury--induced neuropathic pain. Acta Physiol Sin 2005; 57 (5): (in Chinese with English abstract).