Tryptase-PAR2 axis in experimental autoimmune prostatitis, a model for chronic pelvic pain syndrome

Kenny Roman, Joseph D. Done, Anthony J. Schaeffer, Stephen F. Murphy, Praveen Thumbikat*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1328-1338
Number of pages11
JournalPain
Volume155
Issue number7
DOIs
StatePublished - Jan 1 2014

Keywords

  • CPPS
  • Mast cells
  • Pelvic pain
  • Prostatitis

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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