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

Abstract

Chronic itch is a multidimensional physical state strongly associated with emotional and cognitive aspects of suffering that causes the urge to scratch. Pathophysiology, psychological stress, and social milieu can influence itch. Here, we review brain neuroimaging research in humans that detects functional and anatomic changes in health and disease states. New data are emerging that are shaping our understanding of itch mechanisms and scratching-the behavioral response as well as the effect of treatments and brain dynamics during itch. Future developments will continue to expand our knowledge of itch mechanisms, allowing translation to clinical assessment and novel therapies focused on the brain, the final relay of itch transmission.

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

“…[55,[74][75][76][77] In the reviewed fMRI studies, numerous cutaneous itch models perceived itch qualities and response to antipruritic treatments. [75,78,79] C-fibres transmit itch signals to secondary neurons in the dorsal horn, from where they ascend in the contralateral spinothalamic tract to the thalamus, which distributes the signals to the itch-processing brain structures. [73,75] …”

“…[75,78,79] Despite this overlap, cowhage seems to activate a specific set of regions with a pronounced effect on the contralateral insula and claustrum, possibly explaining the more stinging, burning itch quality of cowhage. [79] Figure 3 is an example of a histamine-induced activation pattern.…”

“…Figure 4 is a simplified schematic to characterise the itch network and to outline the function of its structures based on reviewed studies and previous itch reviews. [68,69,78,80] The rudimentary itch network gained from mono-pruritogen itch models in healthy subjects may not reflect real-life conditions of [81] and itch processing is changed due to peripheral and central (alloknesis, punctate hyperkinesis) sensitisation. [70] To define potential treatment targets, the fundamental question therefore is, how is itch centrally processed in patients?…”

“…[68,78,95] FMRI studies of healthy subjects revealed that brain areas involved in affective-motivational and motor planning aspects of itch such as the anterior insular cortex (aIC), basal ganglia (BG), supplementary motor area (SMA), premotor cortex (PM) and cerebellum are activated by visually induced itch. [68,96,97] Moreover, an increased functional connectivity between the aIC and the BG was found during itch imagery, hypothetically linking contagious itch with the corticostriatal circuit mentioned above.…”

“…[95] It has even been speculated that if there is a central source able to produce itch, there must also be a way to reverse the mechanism and produce cure. [78] Placebo effects have not as yet been specifically addressed through fMRI; however, one study reported that nocebo-saline was perceived to be more itchy than open saline and produced a greater response in itch-processing brain regions. [12] Evidence from several non-imaging studies indicates that patients with AD and other chronic itch conditions are particularly susceptible to placebo effects and nocebo effects.…”