The placebo effect in inflammatory skin reactions

Highlights

• Placebo effect demonstrated in inflammatory skin reactions.

• Verbal suggestion can reduce the experience of itch.

• A concrete representation of suggested effects may be important.

Abstract

Purpose

To investigate suggestion-induced placebo effects in inflammatory skin reactions.

Methods

A healthy sample of volunteers (N = 48) attended two laboratory sessions. In each, a local short term inflammatory skin reaction was induced with histamine. Participants were told that one session was a control session and the other was a treatment session in which an antihistamine cream would be applied to the arm to reduce the size of the weal and the experience of itch. Inert aqueous cream was applied in both sessions. Participants were randomly allocated to undergo either the control or the treatment session first.

Results

The placebo manipulation successfully reduced self-reported itch from the control to the placebo treatment session, but no placebo effect was demonstrated in weal size. Order effects were observed such that only those who underwent control procedures first had a smaller weal in the placebo treatment session as compared to the control session. The same order effect was seen for reported itch at one minute post histamine administration, but this disappeared at the three and five minute measures.

Conclusion

Findings suggest that explicit verbal suggestion can reduce the experience of itch. In addition to conscious awareness, a concrete representation of the suggested changes gained from prior experience to the stimulus may be an important component of placebo effects on inflammatory skin reactions.

Introduction

The relative importance of psychological factors in skin conditions such as urticaria continues to be debated [1], but there is empirical evidence to suggest that they can influence the experience of itch [2], [3] and contribute to idiopathic conditions such as chronic spontaneous urticaria [4]. The way an individual thinks and feels appears to impact the status of the skin; however, whether this ‘mind–body’ relationship can be harnessed to ameliorate the symptoms of skin conditions is less clear.

The placebo effect is an intriguing phenomenon in which individuals experience benefit from pharmacologically inert treatments [5]. Expectation, an established mechanism of some placebo effects, is when the patient or participant's expectation of improvement generates real psychobiological changes [6]. Explicit suggestion of benefit is often used to induce expectations, such as providing verbal instructions that a treatment cream will reduce the experience of pain [7]. Placebo-induced expectations are thought to modulate internal homeostatic processes by activating top-down, neurobiological pathways [6], [8]. Thus, placebo research has been described as investigations into the ‘impact of expectations on brain–mind–body interactions’ [9 p. 1922].

While psychological factors are known to influence the immune system [10], there is a paucity of evidence demonstrating that placebo expectancy can exert changes on immune parameters [11]. One possible reason for this is that certain placebo protocols may be more appropriate for the manipulation of certain outcomes. For example, those outcomes of which we are consciously aware (such as pain or motor function) can be influenced by suggestion, unlike those that are not consciously detectable, such as hormone release [12]. Therefore, in order for a suggestive placebo protocol to be effective, a conscious awareness of the suggested changes may be needed [13]. Given the nature of the immune system, this type of awareness is often not possible; however, inflammatory skin reactions can be seen and felt [14], and may be an appropriate target for suggestive placebo protocols.

Only a few studies have attempted to influence inflammatory skin reactions by way of suggestive placebo protocols. One study aimed to reduce histamine induced skin reactions with verbal suggestion and the application of topical ‘anti-histamine’ (placebo) cream [15]. While the manipulation was not successful, the suggestion did not explicitly suggest a smaller weal size or a reduction in perceived itch, but instead a ‘dampened’ response to the histamine. Another study demonstrated a suggestion-induced increase in itchiness, but the suggestion of decreased itchiness was not successful [16]. A recent study demonstrated that while verbal suggestion alone did not modulate itch, placebo effects were demonstrated when suggestion was coupled with a conditioning procedure [17].

While attempts to demonstrate placebo effects in this area have been more successful when conditioning protocols are employed [11], hypnosis (a form of suggestion) can influence immune parameters [18], cognitive-hypnotic protocols have been shown to modulate local inflammatory skin reactions [10], [19], [20], [21], and emotion and arousal mood states can affect hypersensitivity skin reactions [22], [23]. Further, reviews of placebo responses arising from the placebo-control arm of allergy treatment trials found placebo treatments can reduce skin symptoms [24], [25]. The possibility that local inflammatory skin reactions may be modifiable by suggestion alone remains worthy of investigation.

The aim of the current study was to investigate whether a histamine-induced inflammatory skin reaction could be modulated by a suggestive placebo protocol. Explicit suggestions of a reduced weal size and less itching were provided conjointly with a topical ‘anti-histamine’ (placebo) cream. It was hypothesised that when the application of the cream combined with the suggestion of a reduced reaction, participants would experience reduced itchiness and a smaller weal size.