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前扣带皮层NMDA受体-MAPK-CREB通路参与痛厌恶情绪的分子机制

唐雨龙¹, 张玉秋^1,2,*

¹复旦大学脑科学研究院，上海 200032；²复旦大学中西医结合研究院针灸研究所，上海 200032

摘要

疼痛包括感觉分辨和情绪体验两个基本成分。对疼痛感觉分辨成分的研究，在基因、分子、细胞和系统水平已获得重要进展，但对于疼痛的情绪、情感成分的研究相对滞后。越来越多的临床观察显示，疼痛特别是慢性疼痛所伴随的负性情绪状态，严重影响患者的身心健康。本文简要总结了痛厌恶情绪研究领域的主要进展，着重阐述了前扣带皮层(anterior cingulate cortex, ACC)参与痛厌恶情绪过程的神经机制，特别是ACC神经元NMDA受体和ERK-CREB信号通路的关键性作用。多种调控分子如突触相关蛋白SIP30和雌激素可通过突触前和突触后机制调控兴奋性氨基酸释放、NMDA受体功能和ACC锥体神经元突触可塑性参与痛厌恶情绪的形成。

关键词： 疼痛; 痛情绪 ; 前扣带皮层 ; 信号通路

分类号：Q42

Molecular mechanisms of NMDA receptor-MAPK-CREB pathway underlying the involvement of the anterior cingulate cortex in pain-related aversion

TANG Yu-Long¹, ZHANG Yu-Qiu^1,2,*

¹Institutes of Brain Science, Fudan University, Shanghai 200032, China；²Institute of Acupuncture and Moxibustion, Institutes of Integrative Medicine, Fudan University, Shanghai 200032, China

Abstract

The pain experience includes a sensory-discriminative component and an emotional-affective component. The great progress in the genetic, molecular, cellular and systemic levels on the study of the sensory dimension of pain has been made. However, the study of the emotional components of pain is relatively backward. A line of clinic observations indicates that chronic pain and pain-related negative emotion affect the physical and mental health of patients. This review summarizes the main progress from our and other laboratories regarding the affective component of pain, elaborates the neuronal mechanisms of pain-related aversive emotion in the anterior cingulate cortex (ACC), especially the critical role of NMDA receptors and ERK-CREB pathway. A variety of regulatory molecules, such as synapse associated protein SIP30 and estrogen contribute to pain-related aversive emotion via facilitating presynaptic glutamate release and postsynaptic NMDA receptor-mediated synaptic transmission. The far-reaching effects of pain-related negative emotion on patients with chronic pain are emphasized.  

Key words: Pain; pain-related emotion ; anterior cingulate cortex ; signaling pathway

收稿日期：2017-05-04　　录用日期：2017-08-25

通讯作者：张玉秋　　E-mail: yuqiuzhang@fudan.edu.cn

DOI: 10.13294/j.aps.2017.0055

引用本文：

唐雨龙, 张玉秋. 前扣带皮层NMDA受体-MAPK-CREB通路参与痛厌恶情绪的分子机制[J]. 生理学报 2017; 69 (5): 637-646.

TANG Yu-Long, ZHANG Yu-Qiu. Molecular mechanisms of NMDA receptor-MAPK-CREB pathway underlying the involvement of the anterior cingulate cortex in pain-related aversion. Acta Physiol Sin 2017; 69 (5): 637-646 (in Chinese with English abstract).