Brain’s Reward Circuits Mediate Itch Relief. A Functional MRI Study of Active Scratching

Abstract

Previous brain imaging studies investigating the brain processing of scratching used an exogenous intervention mimicking scratching, performed not by the subjects themselves, but delivered by an investigator. In real life, scratching is a conscious, voluntary, controlled motor response to itching, which is directed to the perceived site of distress. In this study we aimed to visualize in real-time by brain imaging the core mechanisms of the itch-scratch cycle when scratching was performed by subjects themselves. Secondly, we aimed to assess the correlations between brain patterns of activation and psychophysical ratings of itch relief or pleasurability of scratching. We also compared the patterns of brain activity evoked by self-scratching vs. passive scratching. We used a robust tridimensional Arterial Spin Labeling fMRI technique that is less sensitive to motion artifacts: 3D gradient echo and spin echo (GRASE) - Propeller. Active scratching was accompanied by a higher pleasurability and induced a more pronounced deactivation of the anterior cingulate cortex and insula, in comparison with passive scratching. A significant involvement of the reward system including the ventral tegmentum of the midbrain, coupled with a mechanism deactivating the periaqueductal gray matter (PAG), suggests that itch modulation operates in reverse to the mechanism known to suppress pain. Our findings not only confirm a role for the central networks processing reward in the pleasurable aspects of scratching, but also suggest they play a role in mediating itch relief.

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

“…[88] Interestingly, stress-imagery activated in particular the hippocampus, which is densely populated with stress hormone receptors [88,122] and involved in the regulation of the HPA axis stress response. [88,122] In another study, only active scratching could deactivate the hippocampus, [91] suggesting that the hippocampus may play a crucial role in coupling stress and scratching behaviour. Both the SA and NSA reduced brain activity but in a different pattern.…”

“…T A B L E 1 List of the 28 PubMed-listed dermatology-related human studies and one case report using fMRI on which this review is based on [97] Itch, contagious itch Healthy subjects [11] Itch, sex differences Healthy subjects [96] Itch and pain, contagious itch Healthy subjects [91] Itch, scratching Healthy subjects [138] Skin picking disorder Skin picking disorder and healthy subjects…”

“…[68] Several studies have reported activation of the reward system including the medial prefrontal cortex, anterior cingulate cortex, striatum, midbrain, also referred to as "cortico-striatal circuit" during pleasurable scratching. [90][91][92][93] Interestingly, activation of motor-related areas (eg SMA, PM and cerebellum) correlates with pleasurability of scratching, even if scratched by experimenters, indicating that pleasurable scratching may promote more scratching. [68] This addictive mechanism seems to be reinforced in chronic itch patients shown to have significantly higher activity in the motor and reward areas during scratching than healthy controls and also perceive scratching non-itchy skin as pleasurable.…”

“…[68,109,110] Data from fMRI studies with healthy subjects, however, are contradictory: in one study, the PAG was activated during scratching, in response to an electrical itch stimulus, [92] whilst in another study, using cowhage, a deactivation of the PAG during scratching was observed. [91] Animal studies demonstrated that apart from this top-down inhibition, ascending itch signals are also suppressed on a spinal level. [68,111,112] FMRI with higher spatial resolution and electrophysiological studies may help to clarify the mechanisms of supraspinal itch inhibition, which could possibly be enhanced as a therapeutic strategy.…”

Neuroimaging of Itch as a Tool of Assessment of Chronic Itch and Its Management

“…Recent findings suggest that the reward system of the midbrain, more specifically the ventral tegmentum (VTA), and substantia nigra, as well as the NAc, may play a role in the urge to scratch and the subsequent satisfaction (pleasure) derived from scratching, via connections with the insula, ACC, and striatum Mochizuki et al 2013Mochizuki et al , 2014. The involvement of VTA and NAc underscores the addictive nature of the itchscratch cycle and also suggests a role for the dopaminergic system in itch relief (Papoiu et al 2013.…”