The Optimal Learning Cocktail for Placebo Analgesia: A Randomized Controlled Trial Comparing Individual and Combined Techniques

Journal of Pain, vol. 24, pp. 2240–2256

Abstract

This study investigated for the first time the effects of individual and combined application of 3 learning techniques (verbal suggestions, classical conditioning, and observational learning) on placebo analgesia and extinction. Healthy participants (N = 206) were assigned to 8 different groups in which they were taught through either a verbal suggestion, a conditioning paradigm, a video observing someone, or any combination thereof that a placebo device (inactive transcutaneous electric nerve stimulation [TENS]) was capable of alleviating heat pain, whereas one group did not (control). Placebo analgesia was quantified as the within-group difference in experienced pain when the placebo device was (sham) 'activated' or 'inactivated' during equal pain stimuli, and compared between groups. Placebo analgesia was induced in groups with 2 or 3 learning techniques. Significantly stronger placebo analgesia was induced in the combination of all 3 learning techniques as compared to the individual learning techniques or control condition, underlining the additional contribution of 3 combined techniques. Extinction did not differ between groups. Furthermore, pain expectancies, but not state anxiety or trust, mediated placebo analgesia. Our findings emphasize the added value of combining 3 learning techniques to optimally shape expectancies that lead to placebo analgesia, which can be used in experimental and clinical settings. PERSPECTIVE: This unique experimental study compared the individual versus combined effects of 3 important ways of learning (verbal suggestions, classical conditioning, and observational learning) on expectation-based pain relief. The findings indicate that placebo effects occurring in clinical practice could be optimally strengthened if healthcare providers apply these techniques in combination.

Authors 8

1. Johan P. A. van Lennep Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University · Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Department of Anesthesiology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Department of Anesthesiology, Amsterdam University Medical Center, Amsterdam, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

2. Henriët van Middendorp Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

3. Dieuwke Swaantje Veldhuijzen Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

4. Kaya J. Peerdeman Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

5. Joseph S. Blythe Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

6. Mia Athina Thomaidou Aachen Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

7. Tom Heyman Aachen Department of Methodology and Statistics Faculty of Social Sciences

   Leiden University

   Affiliation as printed

   Department of Methodology and Statistics, Faculty of Social Sciences, Leiden University, Leiden, the Netherlands

8. Andrea W.M. Evers Aachen Department of Psychiatry, Leiden University Medical Center Health Medical and Neuropsychology Unit Faculty of Social and Behavioural Sciences Leiden Institute for Brain and Cognition Medical Delta

   Leiden University · Leiden University Medical Center · Medical Delta · Delft University of Technology

   Affiliation as printed

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands; Leiden Institute for Brain and Cognition, Leiden, the Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands; Medical Delta, Leiden University, Technical University Delft, and Erasmus University, the Netherlands

   Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands

   Health, Medical and Neuropsychology Unit, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, the Netherlands

   Leiden Institute for Brain and Cognition, Leiden, the Netherlands

   Medical Delta, Leiden University, Technical University Delft, and Erasmus University, the Netherlands