When words hurt: Verbal suggestion prevails over conditioning in inducing the motor nocebo effect

Perception and behavior are strongly influenced by the verbal information conveyed by other individuals (e.g., verbal suggestion) and by learning (e.g., conditioning). This influence is well represented by the placebo and nocebo effects, in which positive verbal suggestion associated with positive conditioning induces beneficial outcomes (placebo effect), while the opposite is true for the negative counterpart (nocebo effect). It is still unclear whether verbal suggestion and conditioning exert distinctive roles in influencing perception, behavior and motor system activity when they occur in opposite directions. To this purpose, fifty-three healthy volunteers were assigned to four groups characterized by either congruent or incongruent verbal suggestion and conditioning. Participants were asked to perform a force motor task by pressing a piston as strongly as possible. Transcranial magnetic stimulation over the primary motor cortex was used to record motor evoked potentials (MEP) and cortical silent period (CSP) from the muscle involved in the task. We found that negative verbal suggestion counteracted positive conditioning and induced sense of weakness, effort, and force decrements. MEP amplitude was stable, whereas the CSP duration shortened in all the groups throughout the procedure, indicating the involvement of cortical inhibitory circuits, independently of the type of verbal suggestion or conditioning. Our findings highlight a prevalent role of verbal suggestion over conditioning in determining a worsening (nocebo effect) but not an improvement (placebo effect) of motor performance. These results suggest that words associated with treatments should be chosen carefully to avoid negative outcomes, especially in sports and clinical settings.