PT - JOURNAL ARTICLE AU - Martin Steinhoff AU - Ulrich Neisius AU - Akihiko Ikoma AU - Manigé Fartasch AU - Gisela Heyer AU - Per S. Skov AU - Thomas A. Luger AU - Martin Schmelz TI - Proteinase-Activated Receptor-2 Mediates Itch: A Novel Pathway for Pruritus in Human Skin AID - 10.1523/JNEUROSCI.23-15-06176.2003 DP - 2003 Jul 16 TA - The Journal of Neuroscience PG - 6176--6180 VI - 23 IP - 15 4099 - http://www.jneurosci.org/content/23/15/6176.short 4100 - http://www.jneurosci.org/content/23/15/6176.full SO - J. Neurosci.2003 Jul 16; 23 AB - 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.