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Summary 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 found 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.

Pruritus is exacerbated at night in many systemic and dermatological diseases, resulting in reports of significantly diminished quality of life and sleep disturbances. At present, the underlying mechanisms responsible for night-time itching are not well understood. Nocturnal pruritus may be related to the circadian rhythm of itch mediators and possibly the disruption of such patterns. Diurnal changes in skin physiology, such as temperature and barrier function, may also play a role. Currently, the paucity of specific treatment options for nocturnal pruritus is alarming and needs to be addressed by future research. This review describes the scale of the problem associated with nocturnal pruritus, the impact it has on patients, possible underlying mechanisms and, lastly, treatment options.

Neuroimaging studies have examined the neural networks activated by pruritus but not its behavioral response, scratching. In this study, we examine the central sensory effects of scratching using blood oxygen level-dependent functional magnetic resonance imaging (fMRI) in 13 healthy human subjects. Subjects underwent functional imaging during scratching of the right lower leg. Scratching stimulus was started 60 seconds after initiation of fMRI acquisition and was cycled between 30-second duration applications of scratching and 30-second duration applications of no stimuli. Our results show that repetitive scratching induces robust bilateral activation of the secondary somatosensory cortex, insular cortex, prefrontal cortex, inferior parietal lobe, and cerebellum. In addition, we show that the same stimulus results in robust deactivation of the anterior and posterior cingulate cortices. This study demonstrates brain areas (motor, sensory, and non-sensory) activated and deactivated by repetitive scratching. Future studies that investigate the central effects of scratching in chronic itch conditions will be of high clinical relevance.

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