Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics

Shawn G. Kwatra, Laurent Misery, Claire Clibborn, Martin Steinhoff

Research output: Contribution to journalReview articlepeer-review


Atopic dermatitis is a chronic inflammatory skin disease. Patients with atopic dermatitis experience inflammatory lesions associated with intense itch and pain, which lead to sleep disturbance and poor mental health and quality of life. We review the molecular mechanisms underlying itch and pain symptoms in atopic dermatitis and discuss the current clinical development of treatments for moderate-to-severe atopic dermatitis. The molecular pathology of atopic dermatitis includes aberrant immune activation involving significant cross-talk among the skin and immune and neuronal cells. Exogenous and endogenous triggers modulate stimulation of mediators including cytokine/chemokine expression/release by the skin and immune cells, which causes inflammation, skin barrier disruption, activation and growth of sensory neurons, itch and pain. These complex interactions among cell types are mediated primarily by cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists of ion channels or various G protein–coupled receptors. Patients with atopic dermatitis have a cytokine profile characterised by abnormal levels of interleukins 4, 12, 13, 18, 22, 31 and 33; thymic stromal lymphopoietin; and interferon gamma. Cytokine receptors mainly signal through the Janus kinase/signal transducer and activator of transcription pathway. Among emerging novel therapeutics, several Janus kinase inhibitors are being developed for topical or systemic treatment of moderate-to-severe atopic dermatitis because of their potential to modulate cytokine expression and release. Janus kinase inhibitors lead to changes in gene expression that have favourable effects on local and systemic cytokine release, and probably other mediators, thus successfully modulating molecular mechanisms responsible for itch and pain in atopic dermatitis.

Original languageEnglish (US)
Article numbere1390
JournalClinical and Translational Immunology
Issue number5
StatePublished - 2022


  • atopic dermatitis
  • cytokines
  • interleukins
  • neuroimmunology

ASJC Scopus subject areas

  • General Nursing
  • Immunology and Allergy
  • Immunology


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