Placebo effects are known phenomena in medical and psychological research. They illustrate how a strong belief can create positive effects regarding well-being and health. However, a strong enough...Show morePlacebo effects are known phenomena in medical and psychological research. They illustrate how a strong belief can create positive effects regarding well-being and health. However, a strong enough negative belief may also have real effects on an individual. This phenomenon is known as a nocebo effect and research into nocebo effects, particularly related to symptoms of itch, has been sparse. Further understanding nocebo itch and its associated brain regions may help patients with chronic itch or psychosomatic afflictions. The aim of this study was to explore the impact of learning and negative outcome expectations on itch sensitivity. We hypothesized that participants would be conditioned to experience more itch in the presence of a sham electrical pulse compared to its absence, and that significant activity would be measured in the periaqueductal gray, insula, and rolandic operculum, which were studied using fMRI imaging techniques. Healthy participants (49) were involved in a two-phase task to acquire and evoke the nocebo itch. This process was reinforced through an on/off monitor and verbal instructions from researchers. In the acquisition phase, participants learned to associate itch stimuli with an electrical pulse (nocebo stimulus), expecting more itch during nocebo trials and less during control trials. Itch was induced using varying histamine concentrations for both types of trials and the electric pulse was never activated. In the evocation phase, nocebo itch was evoked using equal histamine concentrations in both control and nocebo trials. The nocebo itch was measured through subjective itch ratings and brain activity was measured with a 3T fMRI scanner. Evocation nocebo ratings were significantly higher than evocation control ratings, despite equal histamine concentrations (p < 0.001). However, no significant brain activity was found when data from the nocebo condition was compared with the control condition. The absence of conclusive fMRI data may be due to a possible extinction effect nullifying the measurement of nocebo activation, fMRI analysis of areas that were too broad, or overly conservative analysis methodology. These findings indicate the efficacy of the nocebo itch evocation methodology used in this study and future research into additional brain areas associated with nocebo itch.Show less
