识别疼痛恐惧的神经认知机制

Chronic pain lasting more than three months is widespread and has devastating personal and economic costs that are expected to rise sharply, as China's aging population expands and industrialization, modernization, and rural-to-urban migration continue at a rapid pace. In explaining how injuries and acute pain problems become chronic, disabling conditions, the fear-avoidance model (Vlaeyen & Linton, 2000) contends that people who have high fear of pain levels are especially vulnerable due to attention and cognitive appraisal biases related to processing internal and external pain stimuli as sources of threat or potential harm and subsequent avoidance of activity that may cause pain, resulting in physical inactivity, emotional distress and increases in pain. Despite general support for this model, little is known about possible neurocognitive mechanisms that underlie high fear of pain levels. The main purpose of this research is to clarify the nature of these mechanisms in seven studies that include samples of adults (1) who are pain-free, (2) who have acute pain of less than three months duration, and/or (3) have ongoing, chronic, pain. First, we will determine whether the hypervigilance- avoidance attention course observed in our recent eye-movement (EM) tracking studies of attention biases related to fear of pain and chronic pain is a robust attentional pattern underlying fear of pain based on EM-tracking of threatening stimulus words, pictures, and cues for anticipated pain within dot-probe paradigms. Second, we will explore whether high fear of pain corresponds to a distinct profile of ERP responses related to pain images, and anticipated pain compared to low fear of pain. Third, we will extend our published behavior experiments on threat appraisals of pain to fMRI paradigms to evaluate the hypothesis that near-threshold pain sensations appraised as potentially more damaging will be associated with heightened anterior insula-MCC activation and higher pain intensity ratings than near-threshold pain sensations appraised as low in threat (non-damaging) in a sample of pain-free adults. Finally, we will examine whether specific attention biases and profiles of attention bias (e.g., hypervigilance-avoidance pattern) corresponding to high fear of pain levels emerge as risk factors that predict later exacerbations in pain intensity, impairment, and depressive symptoms among acute and chronic pain groups who had previously-completed the EM-tracking research. This research is the first to (1) identify neurocognitive mechanisms underlying fear of pain via assessment of EM, ERP, and neural activation patterns within pain-free and clinical pain groups and (2) evaluate whether patterns of attention biases identified in cognitive-experimental paradigms have utility as potential risk factors for later problems in daily functioning.

慢性疼痛现象非常普遍，已造成个人与社会经济的巨额花费。随着中国老龄化人口的增加，中国工业化、现代化与农村城市化的高速进程，该花费还将迅速增长。恐惧-回避模型提出疼痛恐惧在身体损伤或急性疼痛演变为慢性疼痛、功能丧失中的作用。将疼痛评价为威胁或潜在伤害源，会引起个体回避可能引起疼痛的活动，导致身体活动缺乏、情绪忧郁与疼痛增加。本项目包括：第一，采用眼动研究高疼痛恐惧的慢性疼痛者是否存在警惕-回避注意加工模式；第二，探究高低恐惧者对疼痛图片与预期疼痛的ERP响应差异；第三，采用fMRI研究将疼痛刺激评价为潜在威胁时，前脑岛-扣带回中部的激活水平是否更高。第四，高疼痛恐惧者的注意偏向模式作为风险因子，能否预测慢性疼痛者的疼痛增加、功能损害与抑郁情绪。项目首次采用眼动、ERP和fMRI识别健康与临床疼痛者的疼痛恐惧内在神经认知机制；首次考察注意偏向模式能否作为风险因子，预测疼痛患者后继日常功能问题。

为解释受伤和急性疼痛如何转化为残疾和慢性疼痛，恐惧回避模型（Fear Avoidance Model, FAM; Vlaeyen & Linton, 2000）指出高疼痛恐惧者表现出与疼痛相关的注意和认知评价偏向，进而维持疼痛和功能缺损水平。虽然FAM得到了普遍的支持，但是有关疼痛恐惧或威胁的神经认知机制还知之甚少。为厘清该机制，并识别FAM相关特征和其他认知-情绪因素对疼痛相关结果的预测作用，我们采用眼动追踪，ERP，fMRI，行为实验以及元分析方法，考察非痛被试对实验室诱发急性疼痛和临床被试对术后疼痛以及慢性疼痛的反应。. 眼动研究结果表明，（1）非痛被试和（2）慢性疼痛被试都没有表现出假设中的对高威胁疼痛视觉线索的“警觉-回避”注意模式。相反，相对于低威胁疼痛图片（图片意味着接下来一定没有感觉刺激）来说，两个群体均表现出对高威胁疼痛图片（图片意味着接下来可能会有疼痛刺激）早期的注意朝向和持续的注意警觉。对慢性疼痛被试而言，基线时对疼痛图片（而不是中性图片）持续的总注视时间显著预测6个月后更高的疼痛强度。前期的ERP研究发现，低威胁疼痛图片（描述自身导致疼痛）和高威胁疼痛图片（描述他人导致疼痛）诱发的早期N1波幅无显著差异，但高威胁疼痛图片诱发比低威胁疼痛图片诱发更小的P3波幅。着重考察N2pc成分的ERP研究发现，慢性疼痛被试表现出对情绪面孔（疼痛和高兴）的早期注意偏向，并且，那些表现出对疼痛面孔的早期注意抑制（更小的N2pc波幅）的慢性疼痛被试在6个月后倾向于报告疼痛强度的增加。在fMRI研究中，我们考察了预期近疼痛阈限刺激时的大脑活动。结果表明，与低疼痛恐惧者相比，高疼痛恐惧者报告更高水平的任务恐惧，并在威胁评价和负面情绪加工相关区域（即中部扣带回，中部枕叶皮层，颞极）有更多的激活。但是高、低疼痛恐惧者在所谓的“疼痛矩阵”相关脑区上的激活并无显著差异。. 最后，三个行为实验和4个元分析考察了（1）非痛成年人和大鼠对伤害性刺激的反应，和（2）认知-情绪因素对手术疼痛和慢性疼痛的影响。结果发现，虽然某些FAM特征（威胁评价，疼痛灾难化）能够预测疼痛反应，但是其他因素包括疼痛自我效能具有相当、甚至更重要的预测作用。