Proteinase-Activated Receptor-2 Mediates Itch: A Novel Pathway for Pruritus in Human Skin

• DOI: 10.1523/jneurosci.23-15-06176.2003
• Publication Date: 2018-04-13T22:30:28Z
• Authors: Martin Steinhoff; Ulrich Neisius; Akihiko Ikoma; Manigé Fartasch; Gisela Heyer; Per S. Skov; Thomas A. Luger; Martin Schmelz
• Keywords: Adult; Male; Dose-Response Relationship, Drug; Codeine; Biopsy; Injections, Subcutaneous; Microdialysis; Pruritus; Injections, Intralesional; Immunohistochemistry; Cell Degranulation; Dermatitis, Atopic; 3. Good health; Analgesics, Opioid; 03 medical and health sciences; 0302 clinical medicine; Histamine H1 Antagonists; Humans; Female; Mast Cells; Neurons, Afferent; Oligopeptides; Histamine

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.