健康与遗传心理学研究室知识库

安慰剂效应和反安慰剂效应是心理和生理相互作用的经典实例。当本应无效的物质或处理对个体的身心状态产生积极/消极的影响时，安慰剂/反安慰效应就发生了。由于疼痛给社会和个体造成了巨大的经济和健康负担及对其操纵和测量较为方便，安慰剂效应和反安慰剂效应的研究常常聚焦于疼痛，探讨安慰剂和反安慰剂如何改变个体的疼痛感知及其背后的心理和神经机制。安慰剂效应和反安慰剂效应在理论上有诸多相似之处，如它们产生的机制都涉及经典条件性学习和期望等，但以往的研究显示它们之间似乎也存在着一些重要的差别，如安慰剂效应容易随着时间的演进而消除，而反安慰剂效应却不易消除。然而，反安慰剂消除相关的研究存在一些局限性，其中最重要的一点是:几乎所有声称反安慰剂疼痛过敏难以消除的研究均未使用独立的消退程序，而只是研究了随着时间的变化，反安慰剂效应是否有显著的减弱。这一局限性使得以往研究无法排除一种可能性:单独的消退程序有可能可以消除反安慰剂疼痛过敏。据此，本项研究使用经典条件性学习范式，探索经典消退法消除反安慰剂疼痛过敏的可能性及其神经机制。

研究总共招募79名被试，删除12名因疼痛敏感性异常(过大或过小)的被试后，共有67名被试参与实验。本研究分为四个阶段:阶段一测量被试对接触式热痛刺激的敏感性，并通过90%强化的经典条件反射建立反安慰剂效应;阶段二检测反安慰剂效应是否建立，并根据结果将被试分为建立成功(41人)和失败(26人)两组;阶段三进行消退操作，将反安慰剂效应建立成功组被试随机分为两组:消退组(20人)进行消退任务，控制组(21人)只休息相应时间;阶段四检验消退操作是否成功。同时，本研究还记录了被试对条件刺激后可能跟随的疼痛刺激的预期强度和预期不愉悦度评分，以及在检测反安慰剂效应和消退效果时的脑电数据。

对比消退组和控制组第二阶段检测反安慰剂建立与否时的反安慰剂效应大小和第四阶段消退效果检测阶段的反安慰剂效应大小，可以发现经典消退操作在疼痛强度和不愉悦度两个方面显著降低了反安慰剂效应的大小。除此以外，消退操作也减弱了个体对条件刺激后疼痛刺激的预期强度和预期不愉悦度评分。中介分析结果证实，消退操作对反安慰剂的影响是通过改变个体对条件刺激后疼痛刺激的预期而达成的。对脑电数据的分析显示，消退组在疼痛刺激施加前前额叶和顶枕叶附近电极的a频段能量有显著上升，而控制组则没有明显变化。后续的相关分析表明，刺激前a频段能量上升与预期的变化有密切联系。另一方面，对反安慰剂建立成功组和失败组的对比则显示，利用经典条件反射建立反安慰剂效应时被试对热痛刺激评分的差异与反安慰剂效应的大小有明显相关，因此，非条件刺激在经典条件性学习阶段给个体带来的不同感受可能是反安慰剂效应成立或失败的原因之一。

总的来看，本研究发现经典消退法可以成功减弱反安慰剂疼痛过敏，且个体的心理预期在其中起着中介作用。另外，刺激呈现前a频段能量可能与消退操作的效果相关。这一结果解决了反安慰剂效应是否可消退的争论，为通过消除反安慰剂效应来缓解疼痛提供了证据支持。

Placebo and nocebo effects, the positive and negative effects of inert substance or procedures respectively, exemplify how mind and body interact. They are most oft-studied in the domain of pain (i.e., placebo analgesia and nocebo hyperalgesia) due to the huge health and economic burden of pain. Placebo analgesia and nocebo hyperalgesia have much in common. For example, the psychological mechanisms of them are believed to include expectation, learning一especially classical conditioning 一and many others. However, there seems to be a stark difference in the role of classical conditioning in placebo analgesia and nocebo hyperalgesia. Previous studies have suggested that placebo analgesia is subject to classical extinction, whereas nocebo hyperalgesia is resistant to it. However, most studies about the latter have one particular weakness: no independent extinction procedure is included. As a consequence, previous studies demonstrated only that nocebo hyperalgesia does not diminish over time, not that it is immune to extinction. The present study aims to solve this problem and investigate whether nocebo hyperalgesia is truly extinguishable or not, and the neural mechanisms behind it.

To this end, we recruited 79 participants. The whole study consisted of four sessions. In the first session (Learning Session), we assessed the pain sensitivity using a contact heat stimulator. Due to the abnormal pain sensitivity, 12 participants were removed, leaving 67 participants. They then underwent a learning task, where two squares (conditioned stimuli, CS) were paired with heat stimuli of different intensity (unconditioned stimuli, US). Note that a 90070 reinforcement schedule was employed in this learning task. In the second session (Learn-test Session), we examined whether nocebo hyperalgesia was successfully induced in all of the 67 participants. They were classified as Success or Failure accordingly. Participants marked as Success (41 participants) were then randomly attributed into Extinction Group (20 participants) or Control Group (21 participants). In the third session (Extinction Session), the Extinction Group went through the classical extinction procedure, where the two CS were no longer coupled with painful stimuli, but nonpainful heat stimuli; on the other hand, the Control Group only took a rest. In the final session (Ext-test Session), we tested whether the hyperalgesic effect was extinguished. Note that apart from subject ratings, we also collected EEG data in the Learn-test Session and the Ext-test Session.

Comparing the magnitude of nocebo hyperalgesia of the Extinction Group with that of the Control Group in the Learn-test Session and Ext-test Session, we found that the extinction procedure successfully extinguished the nocebo hyperalgesia in terms of pain intensity and unpleasantness. Moreover, expectation served as a mediation factor in the effect of extinction, which was related to the power increase of a oscillation in the prefrontal and parieto-occipital regions. Additionally, we found that the pain ratings in the Learning Session predicted whether nocebo hyperalgesia was successfully established in the Learn-test Session. By demonstrating that nocebo hyperalgesia can be extinguished using classical extinction, this study offers insight into minimizing nocebo effects and optimizing pain treatment.