Induction and generalization of nocebo effects on itch

Nocebo effects, that is, negative treatment outcomes due to negative expectancies, can increase itch. Moreover, indirect evidence has shown that nocebo hyperknesis can generalize to another itch modality. Knowledge on response generalization can help to prevent and decrease negative effects. The aims of this study were to investigate (1) the efficacy of inducing nocebo effects on cowhage-evoked itch via verbal suggestions and (2) whether these effects can generalize to (2a) mechanically evoked touch and (2b) mechanically evoked itch. Forty-four healthy participants watched a video suggesting that a nocebo solution increases cowhage-evoked itch and that a control solution does not affect itch. Subsequently, cowhage, mechanical itch, and mechanical touch stimuli were applied. Nocebo effects were measured as the difference in both mean and peak of the outcomes itch and urge to scratch between nocebo and control trials. Main analyses revealed significant nocebo effects on mean and peak itch for all stimuli. For urge to scratch, a significant nocebo effect was only observed for mechanical touch (peak). As mechanical stimuli did not induce pure sensations as planned, posthoc sensitivity analyses were run for mechanical stimuli that individually induced either touch or itch at baseline. These analyses showed similar results for generalization to mechanical itch, but generalization to mechanical touch was non-significant. This study showed that merely verbal suggestion can induce nocebo effects on cowhage-evoked itch and that these effects can generalize to another itch modality. Future studies may examine how to prevent negative experiences from generalizing to subsequent encounters.