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[摘要]
慢性疼痛是临床上常见的难题,给人们的生活及工作带来了极大困扰。它是由组织损伤或潜在的组织损伤所引起,发生机制主要有中枢敏化和外周敏化两方面,研究表明中枢敏化过程在慢性疼痛的形成过程中起重要作用。cAMP反应元件结合蛋白(cAMP response element-binding protein,CREB)是一种细胞核内转录因子,通过自身磷酸化激活,对细胞内的信号通路及突触可塑性产生较大的影响,在慢性疼痛中枢敏化形成过程中起重要作用。CREB重要的上游信号分子细胞外信号调节激酶(extracellular signal regulated kinase,ERK)能将细胞外的各种刺激转化为细胞内的不同反应,参与细胞增殖、分化和神经突触可塑性。近年来研究表明ERK-CREB信号通路通过痛觉基因的调控、突触可塑性改变参与中枢敏化的形成。总结了关于ERK-CREB信号通路参与中枢敏化的研究进展、详细阐述了慢性疼痛的基本特点,ERK-CREB信号通路的一般特性及参与中枢敏化的形成,并总结目前ERK-CREB信号通路参与中枢敏化的研究局限,提出研究展望。
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[Abstract]
Chronic pain is a common clinical issue,leading to great burden of people's life.Chronic pain is caused by (potential) tissue damage,and the main hypothesis of it is central sensitization and peripheral sensitization.Studies have proven that the central sensitization process plays an important role in the progression of chronic pain.cAMP response element-binding protein (CREB),a nuclear transcription factor which is activated by autophosphorylation,has a great effect on intracellular signaling pathways and synaptic plasticity,and it is critical in the progression of central sensitization.Extracellular signal regulated kinase (ERK),an important upstream signaling molecule of CREB,can transmit various extracellular stimuli into different intracellular responses,and regulate cell proliferation,differentiation and synaptic plasticity.Recent studies have shown that the involvement of ERK-CREB signaling pathway in regulation of pain-related gene expressions,the changes in synaptic plasticity,and the progression of central sensitization.This review summarizes the advance studies of ERK-CREB signaling pathway in central sensitization,describes the characteristics of chronic pain and ERK-CREB signaling pathway and how it participates in central sensitization.We summarize the limitations of ERK-CREB signal pathway documenting in the central sensitization in current studies and propose research prospects.
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