AUTHOR=Wong Lai-San , Yang Jen-Hau , Yen Yu-Ta , Yang Jenq-Lin 
  
TITLE=Pruritogenic mediators in atopic dermatitis: mechanisms of neurogenic crosstalk
  
JOURNAL=Journal of Cutaneous Immunology and Allergy
  
VOLUME=Volume 9 - 2026
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/journal-of-cutaneous-immunology-and-allergy/articles/10.3389/jcia.2026.16460
  
DOI=10.3389/jcia.2026.16460
  
ISSN=2574-4593
  
ABSTRACT=Pruritus is the most burdensome and persistent symptom of atopic dermatitis (AD), often impairing quality of life more profoundly than visible skin inflammation. Emerging evidence indicates that itch in AD is not merely a downstream consequence of inflammation but an active disease driver that reshapes epidermal barrier integrity and neural plasticity. At the center of AD itch lies a dynamic, bidirectional network linking keratinocytes and sensory neurons. Barrier disruption triggers the release of keratinocyte-derived pruritogens and stress signals that directly activate or sensitize cutaneous nerve fibers, amplifying itch transmission. These epithelial–neuronal interactions are further integrated by intracellular signaling pathways that coordinate environmental and neural inputs. This review synthesizes current mechanistic insights across epidermal and neural compartments and proposes a conceptual framework in which AD itch progresses from peripherally driven signaling to centrally amplified and neurally entrenched states.