• Joseph S Blythe, Mia A Thomaidou, Kaya J Peerdeman, van LaarhovenAntoinette I MAIM0000-0001-6932-9283Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands.Leiden Institute for Brain and Cognition, Leiden, the Netherlands.Department of Psychiatry, Leiden University Medical Cen, Myrthe M E van Schothorst, Dieuwke S Veldhuijzen, and EversAndrea W MAWM0000-0002-0090-5091Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands.Leiden Institute for Brain and Cognition, Leiden, the Netherlands.Medical Delta Healthy Society, Leiden University, Technical Univers.
• Health, Medical and Neuropsychology Unit, Leiden University, Leiden, the Netherlands.
• Pain. 2023 Jun 1; 164 (6): 118111991181-1199.

AbstractPlacebo effects, positive treatment outcomes that go beyond treatment processes, can alter sensations through learning mechanisms. Understanding how methodological factors contribute to the magnitude of placebo effects will help define the mechanisms by which these effects occur. We conducted a systematic review and meta-analysis of experimental placebo studies in cutaneous pain and itch in healthy samples, focused on how differences in methodology contribute to the resulting placebo effect magnitude. We conducted meta-analyses by learning mechanism and sensation, namely, for classical conditioning with verbal suggestion, verbal suggestion alone, and observational learning, separately for pain and itch. We conducted subgroup analyses and meta-regression on the type of sensory stimuli, placebo treatment, number of acquisition and evocation trials, differences in calibrated intensities for placebo and control stimuli during acquisition, age, and sex. We replicated findings showing that a combination of classical conditioning with verbal suggestion induced larger placebo effects on pain ( k = 68, g = 0 . 59) than verbal suggestion alone ( k = 39, g = 0.38) and found a smaller effect for itch with verbal suggestion alone ( k = 7, g = 0.14). Using sham electrodes as placebo treatments corresponded with larger placebo effects on pain than when topical gels were used. Other methodological and demographic factors did not significantly affect placebo magnitudes. Placebo effects on pain and itch reliably occur in experimental settings with varied methods, and conditioning with verbal suggestion produced the strongest effects. Although methods may shape the placebo effect to some extent, these effects appear robust overall, and their underlying learning mechanisms may be harnessed for applications outside the laboratory.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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