These data provide evidence that the visual illusion that an itching limb is being scratched while in fact the non-itching limb contralateral to the itching limb is scratched, can lead to significant itch relief. This effect might be due to a transient illusionary intersensory perceptual congruency of visual, tactile and pruriceptive signals. “Mirror scratching” might provide an alternative treatment to reduce itch perception in focal skin diseases with persistent pruritus without causing additional harm to the affected skin and might therefore have significant clinical impact.

Healthy participants were asked to assess the intensity of an experimentally induced itch at their right forearm while they observed externally guided scratch movements either at their right (itching) or left (non-itching) forearm which were either mirrored or not mirrored. In the first experiment, a mirror placed between the participant’s forearms was used to create the visual illusion that the participant’s itching (right) forearm was being scratched while in fact the non-itching (left) forearm was scratched. To control visibility of the left (non-mirrored) forearm, a second experiment was performed in which unflipped and flipped real-time video displays of the participant’s forearms were used to create experimental conditions in which the participant visually perceived scratching either on one forearm only, on both forearms, or no scratching at all.

The goal of this study was to test whether central mechanisms of scratching-induced itch attenuation can be activated by scratching the limb contralateral to the itching limb when the participant is made to visually perceive the non-itching limb as the itching limb by means of mirror images.

Competing interests: Dr. Helmchen has received speaker honoraria from Thieme Verlag, Pierre Fabre Pharma, GlaxoSmithKline, and Henning Arzneimittel. Dr. Helmchen serves as an editorial board member of Neuro-ophthalmology and Frontiers in Neuro-otology. Dr. Münte is section editor of BMC Neuroscience, co-editor of Frontiers in Language Sciences and Zeitschrift für Neuropsychologie and serves as an editorial board member of Clinical Neurophysiology. This does not alter the authors' adherence to all the Cover Letter PLOS ONE policies on sharing data and materials.

Introduction

Itch can be defined as an unpleasant sensation that provokes the desire to scratch the itching site. Itch is attenuated by scratching. Many inflammatory skin diseases, e.g. atopic eczema, elicit an itch sensation [1] but patients must not scratch the itching skin rashes as skin inflammation might deteriorate. Unfortunately, sustained itch relief is not always achieved by standard drug treatment. Thus, there is a strong need for additional interventions in persistent pruritus.

Histamine reliably elicits itch and a flare by axon reflexes and is therefore used in many experimental human models of itch. In inflammatory skin lesions, histamine is physiologically released by mast cells and activates unmyelinated peripheral C-fibers and spinothalamic lamina I neurons [2-4]. Via spinothalamic afferents these signals are transmitted to brain regions that encode location and intensity of somatosensory sensations , i.e., the primary and secondary somatosensory cortex [5], and valence, i.e., insula and anterior cingulate cortex (ACC) [6].

Under normal conditions, scratching immediately attenuates itch. It has been proposed that scratching-related itch relief is best explained by spinal and supraspinal interactions rather than peripheral receptor-mediated mechanisms [7,8]. For example, excitation of spinothalamic tract neurons by stimulation of the primary afferents by histamine is attenuated by scratching [9]. Itch relief can also be obtained by scratching sites remote from the itching site [10,11] suggesting that central mechanisms may be involved in the control of itch. Scratching does not need to be conducted by oneself but can also alleviate itch when performed by somebody else at the itching or a remote skin area [7].

Driven by clinical demands we sought to establish an experimental condition in which the participant perceives a visible tactile manipulation (scratching) of the non-itching limb to occur on the affected limb. This idea has also recently been proposed in an abstract on phantom itch patients [12]. Altschuler and Scott observed that some patients with itch in a phantom limb noticed phantom itch relief by watching the reflection of scratching on the corresponding intact limb in a mirror [13]. Research in recent years has indicated that multisensory integration can lead to illusionary perceptions in situations that do not normally occur in real-life [14]. For example, observing a mirror image of one’s own limb can lead to the illusionary perception that the mirrored limb is one’s own contralateral limb. A mirror box, placed vertically on the table in front of a subject’s hand, has been used to elicit synaesthesia [15]. When amputees [16] or stroke patients [17] observe their intact limb in a mirror box that is carefully placed parallel to their phantom or paretic forearm this can lead to the illusionary perception that their phantom hand has been resurrected or that their paretic limb is moving [18]. Mirror visual feedback had also been applied to relieve pain in complex regional pain syndrome (CRPS) type 1 [19]. Vision and touch may interact in a way that objects viewed in a mirror are recoded as originating from a location within peripersonal space [20]. Perception in such visuo-tactile conflicts seems to be dominated by visual cues [14]. These examples show that under some conditions, the brain can be “fooled” by multisensory stimulation in a way that stimulations are perceived that do not actually exist. This may elicit visuo- tactile illusions with regard to a person’s self-body schema [14,18,21].

In the current study we sought to extend these findings to the perception of itch attenuation. Unlike mirror visual feedback therapy in motor recovery (e.g. stroke patients) we did not try to elicit the visual impression of bimanual movements but referred sensations in the mirrored forearm. Mirror elicited sensations felt on skin sites which are not physically stimulated, i.e., referred sensations, have been shown in several patient groups, e.g. with stroke [22], CRPS [23], and patients with anesthetic limbs [24]. If CRPS type 1 patients observed tactile stimulations of the mirrored image of their unaffected hand in the mirror they felt allodynia on their affected hand [23]. Stimulation of the unaffected limb elicited referred sensation in the affected limb. In contrast to this aversive allodynia we were looking for an itch-attenuating referred sensation.

We hypothesized that itch relief can be obtained by scratching the limb contralateral to the itching limb if the subject is made to visually perceive the non-itching limb as the itching limb by means of a mirror image. To test this hypothesis, we asked healthy participants to rate the perceived intensity of an experimentally induced, histamine-associated itch before and after they observed externally guided scratch movements either at their itching or their non-itching forearm. Two different experimental approaches were used.

In the first (mirror) experiment, the visual illusion that the participant’s itching (right) forearm was being scratched [while in fact the participant’s non-itching (left) forearm was being scratched] was elicited by means of a mirror, placed in between the participant’s left and right forearm. In the mirror experiment, the participant was instructed to look into the mirror. While this design has a simple and easy-to-implement experimental set-up that makes it suitable for clinical applications, visibility of the non-itching (left) forearm in the mirror condition is not completely controlled. Thus, in order to rule out that any itch attenuation observed in the mirror condition was induced by visual perception of scratch movements on the mirrored and the real left forearm, we run a second (video) experiment. In the latter, unflipped and flipped real-time video displays of the participant’s forearms were used to create experimental conditions in which the participant visually perceived scratching either on one forearm only, both forearms, or no scratching at all. Very recently, video-mediated mirroring of hands had been shown to induce referred sensations equally powerful compared with mirror reflections [25]. We will show that “mirror scratching”, i.e., the visual illusion that an itching limb is being scratched while in fact the non-itching limb contralateral to the itching limb is scratched, can - at least partially - attenuate itch.