Evoked itch perception is associated with changes in functional brain connectivity

Abstract

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray

“…Since itch, like pain, is an aversive sensory experience in humans 17,18,51,59,60 , we hypothesized that pruritogen-evoked itch would produce an aversive state in mice. Here we demonstrate that itch evoked by chloroquine administration resulted in robust conditioned place aversion, in a dose-dependent manner demonstrating that in mice itch is fundamentally an aversive sensation, consistent with recent studies 34 .…”

Itch: From mechanism to (novel) therapeutic approaches

“…In the brain chronic itch modulates activation of particular brain areas, including the ACC, PCC, and PF 82 ; alternates functional brain connectivity 83 ; and can decrease the gray matter in itch-relating cortical areas, including the PF and precuneus. These can play a role in processing the chronification of itch.…”

Addiction and the itch‐scratch cycle. What do they have in common?

“…In the spinal cord, astrogliosis, microgliosis, dysfunction and attenuation of the inhibitory pathways can lead to a state of neuronal hypersensitivity . In the brain, chronic itch such as that involved in atopic dermatitis can lead to functional and structural changes that can perpetuate the sensation of itch …”