Induction and generalization of nocebo effects on itch

In this study on healthy participants, we primarily aim to investigate whether nocebo effects on cowhage-evoked itch can be induced by verbal suggestion. In addition, we test whether nocebo effects can generalize from cowhage-evoked itch to mechanical itch and mechanical touch. The nocebo effects on cowhage-evoked itch will be induced by telling the participants that an ‘itch solution’ will increase the itch sensation evoked by cowhage spicules and a control solution will not affect this itch sensation. In this procedure, alloknesis areas surrounding the cowhage application sites will be measured for each trial. Subsequently, to test generalization, mechanical itch and mechanical touch stimuli will each be applied during six trials: three with the control solution and three with the conditioned solution. This study uses a within-subjects design. Itch ratings and alloknesis areas surrounding the cowhage application sites will be compared between trials in which the supposed ‘itch solution’ or the control solution is applied.

1. The primary objective of this study is to investigate whether nocebo effects on cowhage-evoked itch can be induced by verbal suggestion. We hypothesize that the verbal suggestion that the solution applied is an ‘itch solution’ will induce higher itch evoked by cowhage spicules than the suggestion that it is a control solution.
2. The secondary objective of this study is to test whether nocebo effects generalize from cowhage-evoked itch to mechanically induced itch and to mechanically induced touch. We hypothesize that the verbal suggestion that the solution applied is an ‘itch solution’ will induce higher itch sensations evoked by mechanical stimulations than the suggestion that it is a control solution.
3. Exploratory objectives of this study are 1) to explore whether nocebo effects on cowhage-evoked itch also affect the alloknesis area surrounding the application site and urge to scratch evoked by cowhage. 2) to explore whether nocebo effects generalize to the urge to scratch evoked by the mechanical itch and mechanical touch stimuli. 3) to explore the role of individual characteristics (e.g., anxiety) in the induction and generalization of nocebo effects within itch stimuli and across sensory modalities (i.e., from itch to touch).

All participants will fill out baseline questionnaires to assess demographic and psychological characteristics. After baseline mechanical itch and touch assessments, participants will receive cowhage spicules twice, once with the ‘itch solution’ and once with the ‘control solution’. After each cowhage stimulus, alloknesis areas surrounding the cowhage sites will be assessed with a brush. Following this, they will receive three different mechanical itch stimuli and three different mechanical touch stimuli twice, once with the ‘itch solution’ and once with the ‘control solution’. The whole experiment will take around one and half an hour per participant in a single session.

Participants will receive a verbal suggestion that an ‘itch solution’ will increase the itch sensation evoked by cowhage spicules and that a ‘control solution’ will not affect their itch sensation. In fact, both solutions are water and do not affect itch.