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

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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.