The Role of Tactile Stimulation for Expectation, Perceived Treatment Assignment and the Placebo Effect in an Experimental Nausea Paradigm

Abstract

IntroductionTactile stimulation during a placebo treatment could enhance its credibility and thereby boost positive treatment expectations and the placebo effect. This experimental study aimed to investigate the interplay between tactile stimulation, expectation, and treatment credibility for the placebo effect in nausea.MethodsNinety healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to one of three groups on the second day after the baseline period: Placebo transcutaneous electrical nerve stimulation (TENS) with tactile stimulation (n = 30), placebo TENS without tactile stimulation (n = 30), or no intervention (n = 30). Placebo TENS was performed for 20 min at a dummy acupuncture point on both forearms. Expected and perceived nausea severity and further symptoms of motion sickness were assessed at baseline and during the evaluation period. At the end of the experiment, participants in the placebo groups guessed whether they had received active or placebo treatment.ResultsExpected nausea decreased significantly more in the placebo groups as compared to the no treatment control group (interaction day × group, F = 6.60, p = 0.003, partial η2 = 0.20), with equal reductions in the two placebo groups (p = 1.0). Reduced expectation went along with a significant placebo effect on nausea (interaction day × group, F = 22.2, p < 0.001, partial η2 = 0.35) with no difference between the two placebo groups (p = 1.0). Twenty-three out of 29 participants in the tactile placebo group (79%) but only 14 out of 30 participants (47%) in the non-tactile placebo group believed that they had received the active intervention (p = 0.015). Bang’s blinding index (BI) indicated random guessing in the non-tactile placebo group (BI = 0; 95% CI, −0.35 to 0.35) and non-random guessing in the direction of an “opposite guess” in the tactile placebo group (BI = −0.52; 95% CI, −0.81 to −0.22).ConclusionTactile stimulation during placebo TENS did not further enhance positive treatment expectations and the placebo effect in nausea but increased the credibility of the intervention. Further trials should investigate the interaction between perceived treatment assignment, expectation, and the placebo effect during the course of a trial.

Molecular classification of the placebo effect in nausea

“…Two types of placebo stimulation were applied: 30 participants (15 males, 15 females) received subtle stimulation at a very low intensity by turning on the massage program of the TENS device, while 30 participants (15 males, 15 females) received no electric stimulation at all. Since the two placebo interventions reduced nausea and MS to a similar extent [11], participants from both groups were combined in the present analyses into one placebo group (n = 60).…”

“…Recently, our team completed a randomized controlled trial in healthy volunteers that demonstrated significant placebo effects on symptom ratings in experimentally-induced nausea [ 11 ]. Expanding the findings of this study, we here aimed to identify proteins and associated biological processes that have the potential to track the placebo effect in peripheral plasma.…”

Central correlates of placebo effects in nausea differ between men and women

“…This randomized controlled, four‐arm, parallel group study was conducted at the Institute of Medical Psychology, Ludwig‐Maximilians‐University (LMU) of Munich, Munich, Germany. Full details of the trial participants, design, and results have been previously published (Aichner et al., 2019 ; Meissner et al., 2020 ). In brief, 100 healthy participants were exposed to a virtual vection drum on 2 separate days, referred to as day 1 (control day) and day 2 (intervention day).…”

“…Two types of placebo stimulation were applied: 30 participants (15 males, 15 females) received subtle stimulation at a very low intensity by turning on the massage program of the TENS device, while 30 participants (15 males, 15 females) received no electric stimulation at all. Because the two placebo groups with and without electrotactile stimulation showed comparable effects (Aichner et al., 2019 ), we combined the participants of both groups into one large placebo group ( n = 60) to enhance statistical power. Sensitivity analyses for the EEG parameters were performed to ensure that the two placebo groups were comparable on a cortical level as well (Section 3).…”

Molecular classification of the placebo effect in nausea

“…The purpose of this randomized controlled study was to determine whether the placebo effect can be tracked and predicted by proteins in peripheral blood. Our goal was to develop a method for the reliable and artifact-free verification of placebo effects on clinical endpoints reflecting broadly relevant disease symptoms and chose a well-established model of the placebo effect related to nausea 4,5,6 . In a randomized and carefully controlled design, 90 healthy participants were exposed for 20 minutes to a virtual vection drum on two separate days.…”