Role of Conditioning and Verbal Suggestion in Placebo and Nocebo Effects on Itch

Danielle J P Bartels,Henriët Van Middendorp,Elise A Haverkamp,Andrea W M Evers,Oliver H Wilder-Smith,A Rogier T Donders,Antoinette I M Van Laarhoven,Peter C M Van De Kerkhof,Manabu Sakakibara

doi:10.1371/journal.pone.0091727

Danielle J P Bartels, Henriët Van Middendorp + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0091727

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Abstract

Placebo and nocebo effects are known to play a key role in treatment effects in a wide variety of conditions. These effects have frequently been investigated with regard to pain and also in other physical sensations, but have hardly been investigated with regard to itch. In addition, neither in pain nor in any other physical sensation, the single and combined contribution of the expectancy mechanisms of conditioning and verbal suggestion have ever been investigated in both placebo and nocebo effects within one design. For the first time, the role of verbal suggestion and conditioning in placebo and nocebo effects on itch was experimentally investigated. Expectations about itch stimuli were induced in healthy subjects by verbal suggestion, conditioning, or a combination of both procedures, and compared with a control group without expectation induction. Itch was induced electrically by means of quantitative sensory testing. Significant placebo and nocebo effects were induced in the group in which combined procedures of conditioning and verbal suggestion were applied in comparison with the control group. The conditioning and verbal suggestion procedures applied individually did not induce significant placebo and nocebo effects when compared with the control group. The results of this study extend existing evidence on different physical sensations, like pain, by showing that also for itch, the combination of conditioning and verbal suggestion is most promising in inducing both placebo and nocebo effects. More research on placebo and nocebo effects at a perceptive and neurobiological level is warranted to further elucidate the common and specific mechanisms underlying placebo and nocebo effects on itch and other physical sensations.

Highlights

Placebo and nocebo effects are treatment effects, unrelated to the treatment mechanism, which are induced by patients’ expectations of improvement or worsening respectively [1,2,3]
Patients with atopic dermatitis react more strongly to histamine after nocebo-related itch suggestions [18], and in a previous experiment, we showed that verbal suggestion alone can induce nocebo and possibly placebo effects on itch [19]
Results show that nocebo and placebo effects can be induced on itch, with the strongest effects elicited by a combination of conditioning and verbal suggestion rather than by either procedure alone

Summary

Introduction

Placebo and nocebo effects are treatment effects, unrelated to the treatment mechanism, which are induced by patients’ expectations of improvement or worsening respectively [1,2,3]. Expectation induction mechanisms of verbal suggestion and conditioning have been identified as central processes eliciting placebo and nocebo effects, by decreasing or increasing symptoms respectively, when administering an inert (placebo) treatment or agent [2,13,14]. Verbal suggestion has been shown to induce short-term nocebo effects, whereas conditioning is relevant to induce placebo effects and more robust nocebo effects [13,15,16]. The role of conditioning in placebo or nocebo effects has not been investigated yet, there is some evidence for the role of verbal suggestion in placebo and nocebo effects on itch. Patients with atopic dermatitis react more strongly to histamine after nocebo-related itch suggestions [18], and in a previous experiment, we showed that verbal suggestion alone can induce nocebo and possibly placebo effects on itch [19]

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