Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis
British Journal of Dermatology
Background-Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives-To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods-Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results-We
... nd significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions-Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. Keywords anterior cingulate cortex; arterial spin labelling; atopic dermatitis; functional magnetic resonance imaging; histamine; pruritus 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.