As Different as Fear and Anxiety: Introducing the Fear and Anxiety Model of Placebo Hypoalgesia and Nocebo Hyperalgesia

Abstract

Research suggests that negative affective states, such as fear and anxiety that accompany placebo treatment may be considered predictors of placebo hypoalgesia and nocebo hyperalgesia. There is also data showing that the likelihood of developing nocebo hyperalgesia is related to the relatively stable tendency to experience these negative emotions. We aimed to summarize the current state-of-the-art in studies and theoretical models on the role of fear and anxiety in placebo hypoalgesia/nocebo hyperalgesia, with a clear differentiation between these emotions. The role of fear and anxiety accompanying placebo treatment in shaping placebo effects is often studied, but less attention has been given to pretreatment emotional states. We propose a model that combines knowledge from the emotional and pain paradigms with the current research on placebo hypoalgesia and nocebo hyperalgesia to present the involvement of fear and anxiety as traits, as well as pretreatment and posttreatment states of fear and anxiety to placebo effects. The main assumption of the model is that trait fear, trait anxiety, and related pretreatment affective states impact pain perception differently. Heightened fear is associated with decreased pain perception, while heightened anxiety is linked to increased pain perception. Consequently, heightened pretreatment fear may lead to reduced nocebo hyperalgesia and enhanced placebo hypoalgesia, while heightened pretreatment anxiety may result in decreased placebo hypoalgesia and increased nocebo hyperalgesia. In conclusion, we propose future research directions and clinical applications of the model.