title: Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome.
abstract: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine EAP. Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia led to extracellular signal-regulated kinase (ERK)1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kenny
authors.initials: K
authors.lastname: Roman
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Done
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Schaeffer
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Murphy
authors.forename: Praveen
authors.initials: P
authors.lastname: Thumbikat
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D043422:Carboxypeptidases A / Q000378:metabolism / Q000652:urine; D016022:Case-Control Studies; D059350:Chronic Pain / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism / Q000652:urine; D017699:Pelvic Pain / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism; D011472:Prostatitis / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000378:metabolism*; D015398:Signal Transduction; D053802:Tryptases / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: C502240:NGF protein, human; D044464:Receptor, PAR-2; C509190:Tpsb2 protein, mouse; D020932:Nerve Growth Factor; C468648:CPA3 protein, human; D043422:Carboxypeptidases A; D053802:Tryptases; D002118:Calcium
keywords: CPPS; Mast cells; Pelvic pain; Prostatitis
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