Fig 1.
The study started with negative expectation induction: participants were told that the purple light (conditioned cue) indicated an increase in the itch stimulus, and that the yellow light (neutral cue) indicated no change in the itch stimulus. In accordance with the verbal suggestion, the purple and yellow lights were repeatedly paired with high and medium electrical itch stimulus intensities, respectively. Subsequently, participants were randomized over the three groups in which 1) positive expectations were induced; 2) continued negative expectations were induced; or 3) an extinction procedure was applied. In the learning phases verbal suggestion and conditioning procedures depended on the experimental group. In the testing phase the verbal suggestion corresponded to the verbal suggestion provided in the learning phase, while all participants received electrical itch stimuli of medium intensity. Next, generalization of reduced nocebo effects to histamine application was tested. The verbal suggestion corresponded to the verbal suggestion provided in part 2 and the purple light (conditioned cue) was displayed during the histamine application. The intensity of the histamine application was identical for all groups. Note that for half of the participants the conditioned cue was a purple light and the neutral cue a yellow light (like in this example); for the other half of the participants the conditioned cue was yellow and the neutral purple.
Fig 2.
CONSORT flowchart.
Table 1.
Participant characteristics.
Table 2.
Means (±SD) for itch NRS scores in the learning and testing phase in part 1 (induction of negative expectations).
Table 3.
Means (±SD) for itch NRS scores in the learning phase for the different groups in part 2.
Fig 3.
Means and standard error of the mean (error bars) of the numerical rating scale (NRS) itch scores for the nocebo effect (change in itch NRS score between the four conditioned and four neutral trials) of the different groups in the testing phase of part 2 (higher value indicates higher nocebo effect). The asterisks show the level of significance related to the post hoc Dunnett comparison (***p<0.001; **p<0.01).
Table 4.
Means (±SD) for itch NRS scores in the testing phase for the different groups in part 2.