Nocebo effects are known to adversely affect the experience of various physical symptoms, such as pain and itch. Nocebo effects can be induced by associative learning mechanisms of classical conditioning. Furthermore, recent studies have shown that counterconditioning can successfully reduce nocebo effects, and to a larger extent than mere extinction, which suggests counterconditioning can be an innovative method for desensitization of symptoms. When using such procedures in clinical practice, deception of patients should be avoided as much as possible. The use of open-label procedures could provide a promising alternative. While previous studies have already shown that open-label placebos are effective, the effects of open-label counterconditioning and closed-label counterconditioning are not extensively investigated in comparison to other strategies, such as extinction, and not yet compared amongst each other. Before implementing such a procedure in clinical practice, it would be relevant to get an insight in the efficacy of both open- and closed-label counterconditioning in healthy participants as compared to extinction and to investigate whether open-label counterconditioning can be equally effective as closed-label counterconditioning. Furthermore, it would be relevant to study the induction and reduction of nocebo effects using a pain modality that mimics the type of pain that people suffering from several chronic pain conditions experience, such as pressure pain. The main aim of the current study is to investigate whether open- and closed-label counterconditioning are more effective in reducing nocebo effects than extinction. To this aim, it will be investigated whether open- and closed-label counterconditioning lead to stronger reductions in nocebo effects on pressure pain than (closed-label) extinction, and whether all three successfully reduce nocebo effects. Finally, it will be tested whether open- and closed label counterconditioning are comparable in effectivity.

The primary objective of the study is to investigate whether open- and closed-label counterconditioning are more effective in reducing nocebo effects than extinction.

The experimental (open- and closed-label counterconditioning) and control (extinction) groups will be compared on the change in the nocebo effect from before to after counterconditioning. The nocebo effect is defined as the mean difference in self-reported pain ratings (on a numeric rating scale from 0 (no pain) to 10 (worst pain imaginable))during all experimental trials and control trials in the test phase of nocebo conditioning and the test phase of counterconditioning/extinction. The reduction of the nocebo effect will be determined by calculating the mean difference between the nocebo effect after conditioning and after counterconditioning/extinction. It is expected that participants in both counterconditioning groups will show a larger reduction of the nocebo effect than participants in the extinction group. A one-way ANOVA will be conducted, to examine the main effect of group on the amount of change in nocebo effects. Then, post-hoc analyses will be conducted after the primary analysis, to test for differences between the three forms of nocebo reduction.

Secondary, it will be tested whether all three procedures (open- and closed-label counterconditioning and extinction) lead to a significant reduction of the nocebo effect, by comparing the amount of reduction to test value 0. It is hypothesized that all groups show a significant reduction.

Finally, it will be investigated whether open- and closed-label counterconditioning procedures are comparable in terms of their ability to reduce nocebo effects on pressure pain. Both groups are expected to be comparable in efficacy of reducing the nocebo effect.

Inclusion Criteria:

• Aged 18-35 years
• Good understanding of written and spoken Dutch or English

Exclusion Criteria:

• Severe somatic or psychiatric morbidity (e.g., heart/lung diseases, DSM-V psychiatric disorders)
• Raynaud's disease, chronic pain complaints at present or in the past
• Current pain complaints (> 2 on NRS)
• Current use of medication (except for birth-control pill)
• Injuries on the non-dominant hand
• Refusal/inability to remove nail polish or artificial nails for the experiment
• Pregnancy or breastfeeding

All data are collected pseudonymised; consent forms are the only sources containing personal data and will not be shared, but are monitored by the department's Data Monitor.

Data will become available immediately after study publication and will be retained for 15 years.

Data can be shared with scientists in relevant fields for the purpose of future studies such as replication or meta-analysis (or with designated persons for monitoring purposes).

One of the groups is an open-label group, meaning there is no masking. For the other two groups, participants are not aware of group allocation, but as verbal suggestions are given regarding the device, they are not fully masked (despite being unaware of the procedures that are used).

Investigators are masked until the end of calibration, to prevent the influence of the investigator on the calibration process as much as possible. Afterwards, blinding of the investigator is not possible due to the nature of the study.