Uncovering Cerebral Biomarkers of Itch in Atopic Dermatitis towards Drug Discovery

Itch is the most prevalent and burdensome symptom characterizing atopic dermatitis (AD).1 In contrast with the great progress made unravelling immunologic, genetic, and barrier issues in the skin of patients with AD, little progress has been made in understanding AD itch in an effort to develop topical or systemic mediations that safely combat itch. Ongoing investigations largely focus on understanding itch receptors on cutaneous afferents, but ultimately, the perception of itch requires brain interpretation, which has received virtually no attention. Chronic pain, a similarly complex, multidimensional symptom, provides a helpful parallel and potential blueprint towards a better understanding of AD itch. Neuroimaging-driven investigation into structural and functional changes in chronic pain patients has revealed the central, defining role of the brain in the chronic pain state and uncovered a multitude of unique biomarkers now being applied towards drug discovery.2 Our goal is to leverage this approach to uncover cerebral biomarkers of itch in AD towards development of novel, targeted therapies. Previous neuroimaging studies of itch have suggested that the somatosensory cortex (involved in localization of sensory input and perception of intensity), cingulate cortex (cognition, motivation), medial parietal cortex (memory and attention), insular cortex (emotional awareness, bodily feelings), and motor cortex (preparation and execution of motor movement) are involved in pruritogen responses to varying degrees. However, these observations are based almost exclusively on acute response to pruritogens (e.g., histamine, cowhage) or electrical stimulation, which likely have limited biologic relevance for AD. Itch associated with AD is complex, with heterogenous sensations (e.g., burning, pricking, stinging), varying intensity, and chronic course, none of which can be replicated by an acute, experimental stimulus. To date, no studies have characterized AD itch-driven, stru