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本研究旨在观察脊髓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后第5天,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。
The purpose of this study was to investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in neuropathic pain induced by compression injury of the sciatic nerve. After intrathecal administration of male Sprague-Dawley rats, chronic constriction injury (CCI) was induced by 4-0 silk loosening of the left sciatic nerve. On the fifth day after CCI, different doses of SB203580, a specific inhibitor of p38 MAPK, were intrathecally injected, and von Frey mechanical hypersensitivity monitor and thermal radiation stimulator were used to monitor the rats before administration and at different time points after administration. The threshold of mechanical and thermal stimulation on the injured hind paw was measured. Western blotting was used to observe the changes of phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated cAMP response element binding protein, pCREB) expression changes. The results showed that the p-p38 MAPK protein expression in the spinal cord increased significantly under sciatic nerve compression injury. Intrathecal injection of SB203580 reversed CCI-induced mechanical allodynia and thermal hyperalgesia and spinal cord p-p38 MAPK expression in a dose-dependent manner Significant inhibition of CCI-induced increase of pCREB expression in the spinal cord. The results suggest that p38 MAPK activation at the spinal level is involved in the development of neuropathic pain induced by compression injury of the sciatic nerve and its role may be mediated by pCREB.