Effects of open- and closed label nocebo and placebo verbal suggestions on itch

There is evidence suggesting that negative and positive outcome expectancies
can influence subjective symptoms such as itch. Previous studies show that
negative and positive expectancies can be induced by verbal suggestions and
application of an inert substance (e.g. a cream), and that these in turn might
influence itch sensations. Additionally, although most studies on placebo and
nocebo effects have only informed participants after the study that they
received an inert substance (closed-label placebo/nocebo), there is a growing
body of literature that suggests that placebo effects can occur even when it is
known that a given substance is inert (i.e. open-label placebo). However, no
study to date has investigated open-label nocebo effects, nor has investigated
the efficacy of negative and positive verbal suggestions under both open-label
and closed-label conditions in itch.

The study objective is to assess whether negative and positive outcome
expectations, induced by verbal suggestions under both open-label and
closed-label conditions, can influence self-reported itch during a short-term
validated histamine test.

A randomized, controlled, within-between-subjects study design will be applied.
Participants will be randomly assigned to 1) the closed-label negative verbal
suggestions group, 2) the open-label negative verbal suggestions group, 3) the
closed-label positive verbal suggestions group or 4) the open-label positive
verbal suggestions group. Participants will be invited for a baseline session,
during which they will be exposed to histamine iontophoresis. One week
following the baseline session, participants will be invited to the
experimental session, during which they will receive verbal suggestions and be
re-exposed to histamine iontophoresis. Self-reported itch will be assessed
prior to, during and following histamine iontophoresis. Assessments of
self-reported skin condition, physical parameters (e.g. wheal size, flare
response) and behavioural parameters (i.e. scratching behaviour) will be done
as well. During the baseline session, participants are asked to fill in
additional demographic- and personality questionnaires.

Positive outcome expectations will be induced by verbal suggestions in the
open- and closed-label positive verbal suggestions groups. Negative outcome
expectations will be induced in the open- and closed-label negative verbal
suggestions groups. When suggestions are given under open-label conditions,
participants will receive additional information regarding the effects of
expectations and verbal suggestions on itch.

Participants need to invest a total of maximally 2 hours in the study. Given
the relatively healthy study population, no adverse side effects are expected.
The symptoms of transdermal histamine iontophoresis (local swelling, itch, and
flare) will disappear within several minutes to a maximum of 2 hours. All other
measurements are considered minimally invasive. Participants will receive a
reimbursement of 15,00 euros for participation in this study.