The role of oxytocin on placebo/nocebo effects in a pain conditioning paradigm.

Placebo and nocebo effects have been repeatedly shown to be able to
respectively relief or worsen symptoms of a variety of diseases such as pain,
depression, anxiety, addiction, and Parkinson*s disease amongst others. Despite
an increasing body of literature on placebo effects, it is currently not yet
clear how we can maximize placebo effects in order to obtain the best
therapeutic results and how to weaken the nocebo effects to reduce the side
effects of medications. Oxytocin administration may potentially enhance the
placebo effect by reducing anxiety, increasing trust and stimulating the
secretion of nitric oxide that has been shown to mediate the placebo response.
Only few studies have been performed in this important area with conflicting
evidence.

The primary objective is to investigate whether exogenous oxytocin
administration enhances the placebo effect of as measured by subjective pain
intensity to a previously validated heat pain conditioning task. In addition,
we will explore the effects of oxytocin on the nocebo effect.

A randomized, placebo-controlled study design will be used. Participants will
be randomly allocated to one of two groups: 1) oxytocin group or 2) placebo
group. First, three levels of heat stimulation will be determined for each
participant individually which will be used in the pain conditioning task: 1) a
temperature that elicits low pain (pain detection threshold, equal to around 1
on the 10 numeric rating scale (NRS); low pain), temperature that elicits mild
to moderate levels of pain (equal to around 4 on the 10 NRS, mild pain) and
temperature that elicits moderate to high but bearable levels of pain (equal to
around 7 on the 10 NRS; moderate pain). Afterwards, participants in the
oxytocin group will receive 40 IU of intranasal oxytocin spray; participants in
the placebo group will receive the same volume of a placebo spray. In 30
minutes of waiting time the heat pain conditioning task with conditioning and
testing phases will be performed. Participants in both groups will receive 66
repeated pairings of visual stimuli and pain stimulations and a subjective pain
ratings will be measured. Each stimulus will have a peak temperatures lasting
for 4 seconds.
The experiment will be concluded with filling out several questionnaires and
participants will be debriefed and provided a chance to ask questions about the
experiment and their participation.

In the oxytocin group, participants will receive a 40 IU dose of oxytocin via a
nasal spray. In the placebo group, participants will receive a placebo spray.
The placebo and nocebo effects will be induced by a conditioning procedure
using visual cues and sham electrodes while heat stimuli are delivered.

Study duration will be around 1,5 hours. The study population will consist of
healthy volunteers, therefore, no serious side effects are expected in the
current study. Several studies have been conducted in humans with repeated
doses up to 80 IU of oxytocin without reporting side effects. One time
administration of 40 IU of oxytocin is considered to be a safe and effective
dose.
The standardized pain application device (ATS-II, Medoc Advanced Medical
Systems, Ramat Yishai, Israel) has built-in safeguards and was safely used in
numerous studies on pain stimulation and pain conditioning, including in an
ongoing study of our own group (P15.071). All other measurements are minimally
invasive.
Participants will receive a reimbursement of 15 euros for participation in this
study.