Content » Vol 101, January

Investigative Report

Nocebo Effects on Cowhage-evoked Itch: A Randomized Controlled Trial of Classical Conditioning and Observational Learning

Joseph S. Blythe, Kaya J. Peerdeman, Dieuwke S. Veldhuijzen, Myrthe M.E. van Schothorst, Mia A. Thomaïdou, Antoinette I.M. van Laarhoven, Andrea W.M. Evers
DOI: 10.2340/00015555-3723


To investigate learning processes underlying nocebo effects on itch, this study measured the efficacy of classical conditioning and observational learning for inducing nocebo effects on cowhage-evoked itch and scratching behaviour. A total of 58 healthy female participants were assigned to classical conditioning, observational learning, or sham conditioning groups. In the classical conditioning group, experimenters associated the application of an inert gel with increased itch intensity themselves. In the observational learning group, a video of the conditioning paradigm was shown. Nocebo effects were measured as the difference in itch or scratching between control and nocebo test phase trials, compared between learning and control groups. Compared with sham conditioning, classical conditioning induced a significant nocebo effect on itch, while observational learning did not. No nocebo effect on scratching was detected. These results highlight the role that learning through direct experiences plays in pruritic symptoms. Future research should investigate how a patient’s history of unsuccessful treatments shapes treatment outcomes.


Nocebo effects may occur when we learn to expect something bad will happen, such as our itch getting worse, and then, like a “self-fulfilling prophecy”, the itch really does get worse because we expected it would. This study investigated 2 different ways in which such nocebo effects can occur in healthy participants: learning expectations through direct experience (classical conditioning) and learning expectations through observation (observational learning). While learning through direct experience led to nocebo effects on itch, there were no indications for observational learning having this effect. This suggests that nocebo effects on itch can arise through first-hand, negative experiences with itch treatments.

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