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

Abstract

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.

Neural basis of contagious itch and why some people are more prone to it

“…This shared network includes the anterior insula, premotor cortex, primary somatosensory cortex, and prefrontal cortex. One region not activated in our study but typically activated by chemical induction of itch is the midcingulate cortex, although not all studies of itch have reported activity here (14,29). The magnitude of activation across this "itch matrix" reflects the main effect of viewing itch-related videos (relative to non-itch control stimuli), and tends to correlate with the subjective intensity of itchiness reported for these stimuli.…”

“…The planning of scratching movements is linked to premotor activity, whereas the intention to scratch (or not) is linked to engagement of the prefrontal cortex (12), consistent with this area's recognized role in willed actions (13). Primary and secondary somatosensory cortices have been proposed to support the sensory (i.e., spatial, temporal, and intensity) aspects of the experience (4); however, activity within almost all parts of the itch matrix is correlated with subjective ratings of itch intensity (5,6,14), suggesting interdependence of the sensory, motor, and affective components of itch. Previous fMRI studies were constrained by the methodological limitation that the experience of histamine-induced itch emerges rather slowly, taking approximately 1 min to reach peak intensity after onset of infusion (5), followed by a slow decay.…”

Functional magnetic resonance imaging in dermatology: The skin, the brain and the invisible

“…To date, itch has been studied using fMRI in a small number of patients with atopic dermatitis (AD), [12,[82][83][84][85][86][87] lichen simplex chronicus, [88] prurigo nodularis, [88] end-stage renal disease [89] and psoriasis. [82] Most of these studies were within-subject and placebo-controlled but without direct comparison to healthy controls.…”

Pruritus intensity assessment: challenge for clinicians

“…Several studies have revealed that brain processing of itchy stimuli in patients with chronic pruritus differs from that observed in healthy controls [34][35][36]. Thus, it could be suggested that mapping of brain activity during itch episodes may provide valuable information helping in the assessment of the degree of itch intensity.…”

“…However, current data are rather preliminary, as there is great variability in currently achieved results with different diagnostic techniques. These methods are also too expensive to be used as a routine diagnostic procedure, and thus they are used only for scientific purposes to better understand what happens within the brain upon itchy stimuli [34][35][36].…”