慢性疼痛与皮层-边缘系统

The Role of Corticolimbic Circuitry in Chronic Pain

慢性疼痛作为最常见的临床症状之一,已被认为是全球性的公共健康问题.然而,目前急性疼痛转化为慢性疼痛(即疼痛慢性化)的机制尚不清楚,如何防治急性疼痛转化为慢性疼痛仍然是临床亟待解决的问题.影像学研究表明,编码疼痛情绪、动机和记忆的脑区涉及皮层-边缘系统,而编码持续性疼痛的脑区也主要涉及该系统.基于此,本文概述了慢性疼痛患者在情绪、动机和记忆等方面的行为异常,并详细讨论了慢性疼痛患者皮层-边缘系统的结构和功能变化.其次,本文以慢性腰背痛为例,总结了可能预测疼痛慢性化的影像学指标,如内侧前额叶皮层与伏隔核以及海马的功能连接、背内侧前额叶皮层-杏仁核-伏隔核之间的功能连接均可预测1年后腰背痛疼痛慢性化的发展.此外,基于现有的疼痛慢性化理论模型,本文指出疼痛慢性化可能涉及患者对负面情绪的强化学习以及奖赏和应激系统的功能失调.最后,根据目前研究仍存在的问题和局限,本文对未来的研究方向和方法提出了建议.

Chronic pain is one of the most common clinical symptoms and has been considered as a global healthcare problem.Currently,the underlying mechanisms of the transition from acute to chronic pain,also known as pain chronification,still remain incompletely understood.Neuroimaging studies indicated that the corticolimbic circuitry(prefrontal cortex,amygdala,hippocampus,nucleus accumbens,ventral tegmental area)is preferentially involved in encoding fluctuations of ongoing pain for various chronic pain conditions,suggesting the critical role of this neural circuitry in pain chronification.In this review,we first summarized the emotion,motivation,and memory dysfunctions and their corresponding structural and functional changes of the corticolimbic circuitry in chronic pain patients.Then,we reviewed the longitudinal brain imaging studies on low back pain chronification and highlighted the neuroimaging variables(i.e.,the structural and functional properties of the corticolimbic circuitry)that could predict the transition from acute to chronic pain.For example,the functional connectivity between the medial prefrontal cortex and nucleus accumbens/hippocampus,as well as the functional connectivity between the dorsal medial prefrontal cortex and amygdala/nucleus accumbens could predict the development of chronic pain 1 year later.Besides,based on the existing theoretical model of chronic pain,we emphasized the critical role of the reinforcement learning of negative emotions as well as the dysfunctions of reward and stress systemin pain chronification.Finally,we pointed out the limitations of previous studies in this field and suggested future research directions for a better understanding of the neural mechanisms of chronic pain and pain chronification.