Do open label placebos induce placebo analgesia in a pain conditioning paradigm?

Converging evidence has demonstrated that placebo effects can have a positive influence on pain experience and can be induced by expectations and conditioning. To facilitate applicability of placebo effects in clinical practice, several experimental and clinical studies have demonstrated that it is possible to induce placebo effects even when patients are informed about this (open label placebos), thereby overcoming ethical constraints and facilitate shared decision making. In the current study, a Transcutaneous Electrical Nerve Stimulation (TENS) will be used as a placebo device. Placebo effects will be induced by combining verbal suggestions (about the activation of the TENS device) and conditioning (colored cues paired with low (yellow) and moderate (purple) pain intensities). The main aim of this study is to gain more insight in open label placebo effects. The primary objective is to assess whether open label placebos induce significant placebo effects compared to a control group (no treatment) and the secondary objective assesses whether open label placebo analgesic effects differ from deceptive placebo effects.

The primary aim of the current study is to assess analgesic effects of open label placebos compared to a control group (no treatment). We hypothesize that pain scores rated on a visual analogue scale (VAS) will be significantly lower in the open label placebo group compared to the control group, thereby demonstrating the placebo analgesic effect of open label placebos.
The secondary aim of this study is to compare placebo analgesic effects of the open label placebo group and deceptive placebo group. We hypothesize that there will be no significant difference between VAS pain scores from the open label placebo group and deceptive placebo group.

For exploratory purposes we will also investigate the role of demographics, anxiety and optimism as predictors for the magnitude of placebo effects in a linear regression analysis, as these factors have been associated with placebo effects in previous research findings.

The study consists of an online screening questionnaire, a calibration phase, a conditioning phase, a testing phase and self-report questionnaires on one test day.

Healthy participants will undergo a thermal heat pain procedures in which a series of short heat stimuli are administered. During the calibration phase, individual pain thresholds are assessed for low, moderate and high pain. In the conditioning phase, a sham TENS device of which it is suggested that it affects nerve conductivity will be used as a placebo device and colored cues will be paired with low (yellow) and moderate (purple) pain intensities, combined with verbal suggestions about the activation of the TENS device. Participants in the control group undergo a sham conditioning procedure in which only half of the cues correctly correspond to pain intensities to negate conditioning effects but control for the visual input in the other groups. During the testing phase, all participants receive a moderate intensity of heat stimuli and placebo effects are evoked by presenting the color cues and “TENS ON” or “TENS OFF”.