Effects of emotional context on placebo analgesia and nocebo hyperalgesia in a visceral pain model

将实验安慰剂和反安慰剂研究的知识转移到临床应用的挑战是超越主要的描述性方法，以解决在临床遭遇中如何形成积极和消极的期望。为此，我们旨在阐明积极和消极治疗预期的调节因子，并特别关注消极情绪的作用。可以说，疼痛构成了一个“模型条件”，用于测试关于负面情绪调节安慰剂和反安慰剂干预的特定假设，以解决一个基本问题：“为了患者的利益，安慰剂效应如何最大化，反安慰剂效应如何最小化？”“到目前为止，我们之前在内脏疼痛方面的工作强调了积极和消极预期在塑造对疼痛的反应方面的‘力量’，不仅在行为层面，而且在大脑内部。”与此同时，包括神经内分泌介质在内的外周机制的潜在作用也开始出现。在安慰剂和反安慰剂机制的生物心理社会概念化中，情绪是旨在阐明安慰剂和反安慰剂反应调节因子的研究的主要目标。的确，越来越多的证据支持负面情绪，特别是焦虑，在反安慰剂和安慰剂反应中扮演着重要角色。然而，到目前为止，几乎没有研究直接测试负面情绪对安慰剂和/或反安慰剂反应的影响。因此，我们的目标是解决这样一个假设，即情绪环境影响了安慰剂和反安慰剂在实验性疼痛中的反应。我们建议在健康志愿者中进行一项行为研究，在我们建立的内脏疼痛模型中测试负面情绪的增加和减少对安慰剂镇痛和反安慰剂痛觉过敏的影响。我们预计，由社会心理压力引起的、以焦虑和外周应激介质增加为特征的负面情绪环境，会减少安慰剂镇痛，增加内脏反安慰剂痛觉过敏。同时，我们期望一个积极的情绪环境，由渐进式肌肉放松诱导，以减少焦虑为特征，将增强安慰剂镇痛，减少反安慰剂痛觉过敏。这种关于情绪环境效应的知识将有助于我们理解安慰剂和反安慰剂对实验性疼痛反应的个体间差异。这些知识对于优化医疗干预的治疗环境至关重要，包括医患沟通，而不管使用“真正的”药物治疗还是安慰剂治疗。如果我们的研究结果确实证实了负面环境（即焦虑增加）会减少安慰剂反应并增强反安慰剂反应，那么将安慰剂领域的实验结果引入临床的尝试就必须纳入并系统地考虑患者的情绪状态和特征变量。

The challenge of transferring knowledge from experimental placebo and nocebo research into clinical application is to move beyond primarily descriptive approaches to resolving how in clinical encounters positive and negative expectations are shaped. To this end, we aim to elucidate the modulators of positive and negative treatment expectations with a specific focus on the role of negative emotions. Pain arguably constitutes a ‘model condition’ for testing specific hypotheses about the modulation of placebo and nocebo interventions by negative emotions in order to address the fundamental question: ‘How can placebo effects be maximized and nocebo effects be minimized to the benefit of the patient?’ Thus far, our previous work in visceral pain underscores the ‘power’ of positive and negative expectancies in shaping the response to pain not only at the behavioral level but also within the brain. At the same time, a potential role of peripheral mechanisms, including neuroendocrine mediators, is beginning to emerge. Within a biopsychosocial conceptualization of placebo and nocebo mechanisms, emotions constitute primary targets for research aimed at elucidating the modulators of placebo and nocebo responses. Indeed, there is growing evidence to support a role of negative emotions, specifically of anxiety, in nocebo as well as placebo responses. However, virtually no studies exist thus far which have directly tested effects of negative emotions on placebo and/or nocebo responses. Therefore, our goal is to address the hypothesis that the emotional context shapes both placebo and nocebo responses in experimental pain. We propose to conduct a behavioral study in healthy volunteers testing effects of increased vs. decreased negative emotions on placebo analgesia and nocebo hyperalgesia in our established visceral pain model. We expect that a negative emotional context, induced by psychosocial stress and characterized by increased anxiety and peripheral stress mediators, reduces placebo analgesia and increases visceral nocebo hyperalgesia. In parallel, we expect that a positive emotional context, induced by progressive muscle relaxation and characterized by reduced anxiety, will enhance placebo analgesia and reduce nocebo hyperalgesia. This knowledge about emotional context effects will contribute to our understanding of interindividual differences in placebo and nocebo responses in experimental pain. This knowledge will be crucial for optimizing the therapeutic context in which medical interventions take place, including doctor-patient communication, irrespective of treatment with a ‘real’ drug or a placebo. If our findings would indeed confirm that a negative context (i.e., increased anxiety) reduces placebo responses and enhances nocebo responses, attempts to bring experimental findings from the placebo field into the clinic would have to incorporate and systematically take into account emotional state and trait variables of the patient.