Itch: pathogenesis and treatment.

Abstract

Itch pathogenesis is broadly characterized into histaminergic and nonhistaminergic pathways and transmitted via two main receptor families - G-protein coupled receptors and transient receptor potential channels. In the skin, itch is primarily transmitted by unmyelinated type C and thinly myelinated type Aδ nerve fibers. Crosstalk between the immune and neural systems modulates itch transmission at the skin, spinal cord, and brain. Among the many known pruritogens, Th2 cytokines such as IL-4, IL-13, IL-31, and TSLP are particularly important mediators that signal through shared janus kinase pathways, representing novel targets for novel itch therapeutics. Emerging evidence has also revealed that the opioidergic system is a potent modulator of itch transmission, with increased μ-opioid activity and decreased κ-opioid activity contributing to itch pathogenesis. Optimal management of itch requires tailoring treatment approaches to specific etiological itch subtypes. When the etiology is unknown and patients are given a diagnosis of chronic pruritus of unknown origin, treatment should be guided by the presence of Th2 polarization, often reflected by increased blood eosinophils. In the second article of this two-part series, we outline our current understanding of itch pathogenesis and discuss available and emerging treatments for itch.