Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin.
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.
Steinhoff
Martin
M
Department of Physiology and Experimental Pathophysiology, University of Erlangen, 91054 Erlangen, Germany.
Neisius
Ulrich
U
Ikoma
Akihiko
A
Fartasch
Manigé
M
Heyer
Gisela
G
Skov
Per S
PS
Luger
Thomas A
TA
Schmelz
Martin
M
D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D001706:Biopsy; D015550:Cell Degranulation / Q000187:drug effects; D003061:Codeine / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017551:Microdialysis; D009475:Neurons, Afferent / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011537:Pruritus / Q000209:etiology / Q000503:physiopathology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists / Q000378:metabolism*; D012016:Reference Values; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D053802:Tryptases
D000701:Analgesics, Opioid; D006634:Histamine H1 Antagonists; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; D006632:Histamine; D012697:Serine Endopeptidases; D053802:Tryptases; D003061:Codeine