The following is a summary of “Similarities and differences in peripheral itch and pain pathways in atopic dermatitis,” published in the April 2024 issue of Allergy & Immunology by Yosipovitch, et al.

Atopic dermatitis (AD) is primarily characterized by severe itching, yet a significant proportion of patients also experience skin pain. These patients often exhibit abnormal somatosensory responses, including heightened nerve sensitivity to itch stimuli (hyperknesis), itch perception from harmless stimuli (alloknesis), and pain perception from innocuous stimuli (allodynia). For a study, researchers sought to outline the current understanding of the peripheral mechanisms underlying both itch and pain in AD, highlighting their similarities and differences.

Both sensations share common mediators in the peripheral nervous system, including serotonin, endothelin-1, IL-33, and thymic stromal lymphopoietin. Receptors such as G protein-coupled receptors, Toll-like receptors, and certain transient receptor potential (TRP) cation channels are implicated in signal transduction for both itch and pain. Notably, neurons responsive to itch stimuli also exhibit pain sensitivity.

However, differences exist in the signaling pathways of itch and pain. Pain is associated with specific immune responses involving type 1 and/or type 3 cytokines, as well as certain chemokine C-C and C-X-C motif ligands, while itch is linked to type 2 cytokines like IL-31 and periostin. TRP melastatin channels TRPM2 and TRPM3 are implicated in pain but not itch.

Furthermore, while activation of μ-opioid receptors alleviates pain, it can exacerbate itch. Understanding the interplay between itch and pain mechanisms holds promise for advancing the treatment of chronic pain and itch associated with AD.

Reference: sciencedirect.com/science/article/pii/S0091674923024491