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本文采用大鼠坐骨神经慢性压迫损伤引起的神经病理痛模型,研究脊髓背角细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)在外周神经损伤引起的神经病理疼痛发生中的作用。结果显示,单侧坐骨神经压迫性损伤后1天,大鼠损伤侧脊髓背角ERK的磷酸化(激活)水平显著上调,其下游转录因子cAMP反应原件结合蛋白(cAMP response element binding protein,CREB)在双侧脊髓背角的激活水平也同时上调,而此时由神经损伤引起的痛觉敏化行为尚未出现。神经损伤之前和损伤后早期鞘内给予促分裂原活化蛋白激酶激酶(mitogen-activated protein kinase kinase,MEK)的抑制剂U0126,可阻断和延迟坐骨神经损伤引起的触诱发痛和热痛觉过敏行为的发生。这些结果提示,脊髓背角ERK-CREB信号的激活参与外周神经损伤引起的神经病理疼痛的发生,对该信号通路的早期干预可能是控制神经病理性疼痛的重要手段。
In this study, we used a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve to investigate the role of extracellular signal-regulated kinase (ERK) in the neuropathic pain induced by peripheral nerve injury. The results showed that the level of phosphorylation (activation) of ERK in the dorsal horn of spinal cord on the injured side of the unilateral sciatic nerve was significantly increased one day after compression injury, and the downstream transcription factor cAMP response element binding protein (CREB) Activation of both spinal dorsal horn also increased at the same time, but at this time caused by nerve injury pain sensitization behavior has not yet appeared. U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK), intrathecally administered before and after nerve injury, can block and delay the traumatic and thermal hyperalgesia induced by sciatic nerve injury occur. These results suggest that activation of ERK-CREB signaling in spinal dorsal horn is involved in the development of neuropathic pain induced by peripheral nerve injury. Early intervention of this signaling pathway may be an important means of controlling neuropathic pain.