[關(guān)鍵詞]
[摘要]
慢性疼痛是臨床上常見的難題,給人們的生活及工作帶來了極大困擾。它是由組織損傷或潛在的組織損傷所引起,發(fā)生機(jī)制主要有中樞敏化和外周敏化兩方面,研究表明中樞敏化過程在慢性疼痛的形成過程中起重要作用。cAMP反應(yīng)元件結(jié)合蛋白(cAMP response element-binding protein,CREB)是一種細(xì)胞核內(nèi)轉(zhuǎn)錄因子,通過自身磷酸化激活,對(duì)細(xì)胞內(nèi)的信號(hào)通路及突觸可塑性產(chǎn)生較大的影響,在慢性疼痛中樞敏化形成過程中起重要作用。CREB重要的上游信號(hào)分子細(xì)胞外信號(hào)調(diào)節(jié)激酶(extracellular signal regulated kinase,ERK)能將細(xì)胞外的各種刺激轉(zhuǎn)化為細(xì)胞內(nèi)的不同反應(yīng),參與細(xì)胞增殖、分化和神經(jīng)突觸可塑性。近年來研究表明ERK-CREB信號(hào)通路通過痛覺基因的調(diào)控、突觸可塑性改變參與中樞敏化的形成??偨Y(jié)了關(guān)于ERK-CREB信號(hào)通路參與中樞敏化的研究進(jìn)展、詳細(xì)闡述了慢性疼痛的基本特點(diǎn),ERK-CREB信號(hào)通路的一般特性及參與中樞敏化的形成,并總結(jié)目前ERK-CREB信號(hào)通路參與中樞敏化的研究局限,提出研究展望。
[Key word]
[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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