Can nocebo effects on itch be modified by a positive expectation induction?

For highly prevalent conditions associated with chronic itch, treatment effects
are usually modest and vary strongly across patients. Expectancy mechanisms may
contribute to this variability. The influence of expectations have often been
studied in a placebo- or nocebo design, in which expectations are, for example,
induced by verbal suggestions or a conditioning procedure. Placebo and nocebo
effects can be defined as favorable and unfavorable treatment responses,
unrelated to the treatment mechanism, which are induced by expectations of
improvement and worsening, respectively. Placebo and nocebo effects have been
investigated primarily in studies that focus on pain. Recent research of our
research group showed in a validated design that expectancy mechanisms of
verbal suggestion and conditioning can also induce placebo and nocebo effects
on itch. However, it is not yet known whether nocebo effects can also actively
be modified, e.g., by inducing a positive expectation induction, resulting in
less itch. This is a scientifically and clinically highly relevant research
question for the development of treatment modules to change inadequate negative
expectations of patients suffering from chronic itch complaints.

The main objective of the study is to determine whether induced nocebo effects
(negative expectancy effects) for itch can be modified by a positive
expectation induction. Secondary objectives are to explore: a) the effects of
expectation inductions on scratching behavior, b) the generalization of
expectancy effects to other types of itch stimuli, c) the role of individual
characteristics on expectancy effects, and d) the role of genetic
predispositions on expectancy effects.

In healthy subjects, expectations with regard to electrically evoked itch will
be induced by a conditioning with verbal suggestion procedure, in
correspondence to a previous experiment conducted by the research group. For
every stimulus, participants are asked to report the level of itch on a Visual
Analogue Scale (VAS), and the scratching behavior of the participants will be
recorded during the experiment. In part I, in all participants high-itch
expectations will be induced (nocebo induction). More specifically, in the
learning phase, short-lasting itch stimuli of medium and high intensity are
repeatedly associated with certain colored cues displayed on a computer screen
(e.g., two colored cues of which one cue is associated with itch stimuli of
medium intensity (neutral cue), and the other with itch stimuli of high
intensity (conditioned cue)). In line with the conditioning procedure, verbal
suggestions for high itch will be given regarding itch stimuli associated with
the conditioned cue. Subsequently, in the testing phase, expectancy effects for
itch with regard to the colored cues will be tested by applying both the
conditioned and neutral cues with itch stimuli of medium intensity. In part II,
participants will be randomly assigned to one of three groups: the experimental
group, in which low-itch expectations will be induced (group 1) (similar to the
procedure described above with the exception that the conditioned cues are now
associated with low itch intensity stimuli), a control group in which once more
high-itch expectations will be induced similar to part I (group 2), or a
control group with a neutral itch induction procedure (neutral expectation
induction) (group 3). In part III, generalization of the induced expectancy
effects will be tested with respect to another itch stimulus, i.e., histamine
iontophoresis.

Participants will complete a series of validated questionnaires at home to
assess relevant individual characteristics, for approximately half an hour.
Participants will then visit the department of Clinical, Health &
Neuropsychology at the Leiden University once for approximately 4,5 hours.
Sensations of itch will be induced using frequently applied and by the research
group validated stimuli of short duration which are not burdensome. DNA is
collected by asking participants to spit in a special tube. No risks are
involved with participation in this study, only an investment of time.