Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis.

Pruritus is a most distressing symptom in many dermatological and systemic disorders – the most notable being atopic dermatitis (AD).1 In its chronic form, pruritus profoundly impacts quality of life and constitutes an enormous burden to society. Pruritus is so central to AD that it may frequently be referred to as ‘the itch that rashes’.2 Currently, the understanding of the pathophysiology of pruritus is poor. Present data points towards an intricate interplay between peripheral and central mechanisms.3 Neuroimaging studies until recently were focused on brain imaging of histamine-induced itch in healthy human subjects. In healthy humans, acute histamine-induced itch coactivates the anterior cingulate cortex (ACC), the insular and primary somatosensory cortices, premotor and supplementary motor areas, cerebellum and thalamus.4–13 A recent study using positron emission tomography (PET) was the first to image brain processing of itch in patients with AD in remission and demonstrated similar areas of activation to those of healthy subjects, with higher activation in patients with AD in the contralateral thalamus, ipsilateral putamen and pallidum.14 However, as yet there is no study that has examined brain activation of itch in patients with active chronic itch. The neuroimaging of pruritus-related brain activity is a methodogical challenge. To date, studies have used PET and functional magnetic resonance imaging (fMRI) employing blood oxygen level dependent (BOLD) contrast.4,5,7,9,10,12 Although PET is fully quantifiable, radiation exposure and methodological complexities associated with this neuroimaging technique limit its routine use. In addition, the BOLD technique is suited to a biphasic stimulus model where sensory stimuli are turned on and off within a few seconds. However, the biphasic stimulus model is not suitable for experimentally induced itch, which usually takes a few minutes to reach peak intensity. Recent studies have been performed to overcome this limitation by manipulating the time course of itch with repeated itch induction with intermittent cooling or local anaesthetics.6,11 These experimental designs are rather complex to perform. The emerging technique of fMRI using arterial spin labelling (ASL) appears more suited to assess pruritus-related brain activity than the widely adopted BOLD method. Reasons include improved sensitivity for slow changes in neural activity (> 30 s) and better comparisons between different subject groups.15,16 In the present study we evaluated the central processing of histamine-induced pruritus in patients with AD with active disease and healthy subjects using the emerging technique of ASL fMRI. We show that the neural networks activated by pruritus differ in these two groups.