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.@en

Background: Nocebo and placebo effects, i.e., adverse or beneficial treatment effects, respectively, putatively due to expectancies can modulate pain and itch. These effects can generalize within the pain or itch modality. Predicting the induction and generalization of these effects can be helpful in clinical practice. This study aims to investigate whether psychological characteristics related to the fear-avoidance model predict the induction and generalization of nocebo and placebo effects on pain and itch in young healthy participants. Methods: Data from two previous experiments were analyzed. In Experiment 1, we induced nocebo and placebo effects on heat pain and tested generalization to pressure pain and to cowhage-evoked itch (n = 33 in a nocebo group, n = 32 in a placebo group). In Experiment 2, we induced nocebo effects on cowhage-evoked itch and tested generalization to mechanical itch and to mechanical touch (n = 44). Potential predictors were anxiety- and stress symptoms, attention to pain/itch, and pain/itch catastrophizing. Multiple regression analyses were performed. Results: For nocebo effects, none of the individual psychological characteristics significantly predicted induction of nocebo effects nor their generalization. For placebo effects, only less stress symptoms, lower attention to pain, and higher pain catastrophizing weakly predicted a stronger generalization of placebo effects from heat pain to pressure pain. Conclusion: The tested psychological characteristics may not play an important role in the induction and generalization of nocebo and placebo effects in healthy individuals. However, firm conclusions cannot be drawn with the current sample. Future studies should validate findings in larger and more diverse samples.@en

Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. Our aims were to test whether placebo and nocebo effects can generalize within pain modalities, ie, from heat pain to pressure pain, and across somatosensory sensations with psychophysiological similarities, ie, from heat pain to cowhage-evoked itch. For this purpose, 65 healthy participants were randomized to either a placebo or nocebo group. All participants first underwent a conditioning and verbal suggestion procedure with heat pain stimuli. Subsequently, responses to heat pain, pressure pain, and cowhage-evoked itch stimuli were tested. Results showed altered levels of heat and pressure pain with the conditioned cue in both placebo and nocebo groups in the expected directions, but no significant difference in itch in both groups. In conclusion, placebo and nocebo effects on pain may generalize within but not across stimulus modalities. This study provides a novel perspective on the role that response generalization plays in physical symptoms.@en