吸烟戒断诱发疼痛敏感性升高的大脑影像学研究

Clinical studies demonstrated that smoking abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression. In addition, these side effects would hinder patients’ physical and psychological recovery. Unfortunately, the mechanism, especially the neural mechanism, of increase in pain sensitivity induced by smoking abstinence remains unknown. Comparing smoking addicts with non-smoker controls, this project will jointly utilize smoking withdrawal behavioral scales, magnetic resonance imaging, and pain sensitivity measurement techniques to solve the following issues. First, we will investigate the relationship between smoking withdrawal behaviors (psychological characteristics including craving, anxiety, depression, etc.) and pain sensitivity, and extract behavioral predictors of pain sensitivity during smoking abstinence. Second, we will investigate brain structural and functional abnormalities in abstinent smokers using multimodal neuroimaging analysis methods, and examine the relationship between these abnormalities and pain sensitivity. In addition, to reveal the neural mechanism of smoking abstinence-induced increase in pain sensitivity, the project will systematically assess the relationship among "smoking withdrawal behaviors", " brain structural and functional abnormalities", and "pain sensitivity" to establish a theoretical and predictive model of abnormal pain sensitivity in abstinent smokers. This project will provide theoretical guidance for the effective assessment, management, and intervention of clinical pain for smoking abstinent individuals, which would have high scientific value and broad prospects in clinical applications.

临床研究发现吸烟戒断患者的痛阈降低，疼痛敏感性升高。接受手术治疗的吸烟戒断患者对阿片类镇痛药物需求大大增加，造成了恶心呕吐、呼吸抑制等副作用，阻碍了患者的身心康复。然而，吸烟戒断诱发疼痛敏感性升高的机制，尤其是脑神经机制，尚不清楚。本项目以吸烟成瘾者和不吸烟者为研究对象，结合吸烟戒断行为量表、磁共振成像及疼痛敏感性测量等技术，（1）考察吸烟戒断行为（渴求、焦虑和抑郁等心理特征）与疼痛敏感性的关系，提取戒断状态疼痛敏感性的行为预测指标；（2）采用多模态影像学分析方法，研究吸烟者戒断状态脑结构与功能异常，考察这些异常与疼痛敏感性的关系，揭示吸烟戒断诱发疼痛敏感性升高的脑神经机制。本项目还将系统分析“吸烟戒断行为”、“脑结构与功能异常”和“疼痛敏感性”的关系，构建戒断状态疼痛敏感性异常的理论和预测模型。本项目将为吸烟戒断患者疼痛的有效评估、管理和干预提供理论指导，具有较高的科研价值和应用前景。

吸烟戒断者的疼痛敏感性升高，吸烟者患慢性疼痛的风险显著高于不吸烟者。因此，本项目旨在探究吸烟戒断诱发疼痛敏感性升高的脑神经机制；研究慢性疼痛的心理生理机制；探索非药物镇痛疗法的机制及临床应用，为缓解吸烟者的疼痛提供干预治疗方案。围绕以上问题，本项目开展了多方面的研究：（1）揭示了吸烟者满足状态的脑功能网络连接异常（Wang et al., 2020），总结了吸烟者戒断后的心理生理变化及其脑功能基础（Bi et al., 2021）；（2）综述了尼古丁成瘾及戒断后疼痛敏感性的变化趋势及疼痛刺激类型对此变化趋势的影响，总结出尼古丁戒断后脑内相关神经递质的释放及其受体的激活的变化对其疼痛敏感性的影响（钟嘉慧等，2021）；（3）对慢性疼痛的最新影像学研究成果进行综述，提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（王飞雪等，2020），并对几种慢性疼痛引起的大脑改变进行了荟萃分析，系统总结了整合机器学习和神经影像技术来识别慢性疼痛患者的诊断、预后和预测性生物标志物的新兴研究（Tu et al., 2020）；（4）发现常规型和针刺样经皮神经电刺激的镇痛效果不同，且受不同的脊髓上神经机制调节（Bi et al., 2020）。通过对临床研究的最新成果进行总结，提出通过给予优化的刺激参数，经皮神经电刺激可以有效的缓解患者的神经性疼痛（Mokhtari et al., 2020）。此外，本项目发现了激光诱发的疼痛感知和脑响应在不同的时间段存在变异性（Bi et al., 2021）及负性情绪在疼痛敏感性性别差异中的作用及脑机制（Zhang et al., 2021）。综上，本项目加深了我们对吸烟戒断诱发疼痛敏感性升高的脑机制及慢性疼痛心理生理机制的认识，同时证明了经皮神经电刺激镇痛的有效性，有助于促进基础研究向临床应用的转化。