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

将知识从实验性安慰剂和NOCEBO研究转移到临床应用的挑战是超越主要的描述性方法，解决临床遭遇中积极和消极预期是如何形成的。为此，我们的目标是阐明积极和消极治疗期望的调节器，特别关注消极情绪的作用。可以说，疼痛构成了测试关于负面情绪对安慰剂和非安慰剂干预的具体假设的一种“模型条件”，以解决一个基本问题：“如何才能最大化安慰剂的效果，而将非安慰剂的影响降至最低，以造福于患者？”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”，不仅在行为层面上，而且在大脑内也是如此。与此同时，包括神经内分泌介体在内的外周机制的潜在作用开始显现。在对安慰剂和不服用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不服用安慰剂反应的调节剂的主要研究目标。事实上，越来越多的证据支持负面情绪，特别是焦虑情绪在不服用安慰剂和服用安慰剂的反应中所起的作用。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/或非安慰剂反应的影响。因此，我们的目标是解决这一假设，即在实验性疼痛中，情绪环境塑造了安慰剂和非安慰剂反应。我们建议在健康志愿者中进行一项行为研究，测试在我们建立的内脏疼痛模型中，增加和减少负面情绪对安慰剂止痛和痛觉过敏症的影响。我们预计，由心理社会压力引起的以焦虑和外周压力介质增加为特征的负面情绪环境，会减少安慰剂止痛，增加内脏痛觉过敏。同时，我们预计积极的情绪环境，由渐进性肌肉放松诱导，以减少焦虑为特征，将增强安慰剂止痛和减少痛觉过敏。这些关于情绪情境效应的知识将有助于我们理解在实验性疼痛中安慰剂和非安慰剂反应的个体间差异。这些知识对于优化医疗干预的治疗环境至关重要，包括医生与患者之间的沟通，而不考虑是否使用“真正的”药物或安慰剂进行治疗。如果我们的发现确实证实了负面背景(即，增加的焦虑)会减少安慰剂反应，增强非安慰剂反应，那么将安慰剂领域的实验结果带入临床的尝试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.