自发/诱发疼痛中的神经振荡同步性及其对疼痛的调控机制研究

Pain is the main symptom of multiple clinical diseases, which not only brings physical discomfort to people, but also influences people's spirit, psychology and working life. Research on pain mechanisms and analgesic strategies helps to address the growing problem of pain, improve people's physical and mental health, and increase people's quality of life. It has been shown that stimulus evoked pain information processing involves the synchrony of neuronal oscillations in multiple frequency bands and brain regions, and the development and persistence of chronic spontaneous pain is relevant with the abnormality of neuronal oscillations. Understanding the functional significance of neural oscillations in the cognitive process of pain will help expand the theory of pain mechanisms, and potentially will be used in the diagnosis and treatment of chronic pain. With the application of psychophysical measures, neuroimaging and bio-feedback techniques, the present project propose to undertake the following studies from the aspects of basic mechanism and clinical applications: (1) investigating the association between spontaneous/evoked pain and neuronal oscillations, extracting neuronal oscillatory features that could predict individual pain experience and identifying their basis of brain structural and functional network; (2) establishing a bio-feedback system for pain relief, based on the modulation of neuronal oscillations, which validity would be further confirmed on the chronic pain management. The outcome of this project will not only shed light on the dynamic brain mechanisms underlying subjective pain perception, but also promise to relieve pain from patients in the clinical application, thus achieving the aim of effective control of pain.

疼痛是多种临床疾病的主要症状，它不仅给人们带来身体上的不适，还影响着人们的精神、心理、工作生活等诸多方面。疼痛机制和镇痛策略的研究有助于解决日益突出的疼痛问题，改善人们的身心健康、提高人们的生活质量。已有研究表明：刺激诱发疼痛的信息处理过程涉及多个脑区和多个频段神经振荡的同步化，且慢性自发疼痛的发展与持续和神经振荡的异常有关。理解神经振荡在疼痛认知过程中的功能有助于拓展疼痛机制理论，还有望用于慢性疼痛的诊断与治疗。本项目拟运用心理物理测量、神经影像和生物反馈技术，从基础研究和临床应用两方面展开：（1）分别研究自发/诱发疼痛与神经振荡之间的联系，提取能预测疼痛的神经振荡及其同步性特征，并探明其对应的脑结构与功能基础；（2）建立基于神经振荡调控的镇痛生物反馈系统，验证其对慢性疼痛缓解的有效性。本项目的开展将促进深入认识疼痛认知过程中的动态脑机制，还有望促进慢性疼痛的缓解，实现对疼痛的有效控制。

疼痛是由感觉与情境（包括认知、情绪和动机）动态相互作用导致的综合现象，其信息处理过程涉及多个脑区及多个频带神经振荡的同步化。提取并调控这些与疼痛有关的神经振荡活动将可能实现对疼痛的有效缓解。为认识疼痛的脑神经振荡机制，本项目首先以健康被试为研究对象，从情绪和社会认知层面探讨了疼痛相关的神经振荡及其同步性特征，然后以辣椒素诱发的长时疼痛模型，结合脑电和功能磁共振技术，探讨了实验性长时疼痛的神经振荡和宏观脑网络机制，最后以慢性疼痛患者为研究对象，探索了慢性疼痛下大脑自发神经振荡活动的异常，提取了临床自发疼痛有关的神经振荡特征。结果发现疼痛的情绪和社会认知加工过程涉及不同频带神经振荡响应特征：观察图片诱发的替代性疼痛诱发顶叶α神经振荡的减弱，社会疼痛诱发前额叶Ɵ神经振荡的增强。实验性诱发疼痛和临床自发疼痛下的神经振荡模式表现出差异：辣椒素诱发疼痛会减弱Ɵ和α频段下背侧注意网络的局部和全局效率，增强默认模式区域与听觉、视觉和体感区域之间的功能连接；持续性躯体疼痛患者的顶叶区域表现出更强的α神经振荡，且这一频带下的额-顶叶功能连接性更强。为有效缓解疼痛，本项目采用经皮神经电刺激、经颅电刺激（经颅直流电/交流电/随机噪声刺激）、神经反馈技术以及认知策略（以预期为例）调控疼痛有关的α神经振荡特征，通过心理物理测量、脑电和功能磁共振技术考察调控前后的疼痛敏感性和大脑功能状态，探索了基于大脑神经振荡调控对疼痛缓解的效果及其神经生理机制。研究结果表明提升感觉运动皮层α神经振荡能通过减低感觉运动皮层对疼痛的神经响应从而间接缓解疼痛体验，还会降低感觉运动皮层与疼痛处理相关脑区之间的功能连接，包括中间扣带皮层、对侧体感皮层和背外侧前额叶皮层。本项目的研究成果不仅有助于深入理解疼痛知觉形成过程中的大脑神经振荡机制，还有望应用于临床镇痛，帮助缓解患者痛苦，提高患者的生活质量。