Behavioral and neural underpinnings of positive and negative treatment expectations, and their effects on pain - Trial DRKS00031993

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Summary

Pain can be modulated by positive and negative expectations, which is also referred to as placebo analgesia/hypoalgesia and nocebo hyperalgesia, respectively (Benedetti et al., 2022; Colloca & Barsky, 2020). While the effects of positive expectation (placebo analgesia) are generally well researched regarding their underlying neurobiological mechanisms, rather little is known regarding the effects of negative expectations on pain processing (nocebo hyperalgesia). Furthermore, more research is needed on a direct comparison of both of these effects in the same paradigm and in the same people. This study thus investigates how positive and negative treatment expectations influence the neural processing of nociceptive information and the subjective perception of pain in healthy volunteers. The main goal is to elucidate the common and distinct (neural) mechanisms underlying positive and negative expectations, and their influence on pain processing in two phases: 1) the expectation formation during conditioning with experimental reinforcement of positive or negative treatment experience and 2) a placebo analgesia / nocebo hyperalgesia test session without such reinforcement. To this end, we will investigate the temporal dynamics and neural mechanisms underlying the formation and effects of positive and negative expectations in an established model of conditioned placebo hypoalgesia/nocebo hyperalgesia (see Colloca et al., 2010) using a within-subject design and funktional magnetic resonance imaging (fMRI) . The main outcomes are expectancy ratings, pain ratings and neural responses to cued thermal pain stimuli. Furthermore, exploratory outcome measures, their association with individual expectations and their effects on pain (placebo/nocebo effects). These include, among others, psychological state and trait measures, functional and structural brain connectivity (resting-state fMRI, Diffusion Tensor Imaging, etc.), as well as genetics (including polymorphisms previously associated with placebo effects (Hall et al., 2015) and exploratory genome-wide association studies (GWAS).

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