802 CHRONIC PELVIC PAIN IS ASSOCIATED WITH MAST CELL ACTIVATION AND IS AMENABLE TO MAST CELL DIRECTED THERAPIES

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 2010802 CHRONIC PELVIC PAIN IS ASSOCIATED WITH MAST CELL ACTIVATION AND IS AMENABLE TO MAST CELL DIRECTED THERAPIES Praveen Thumbikat, Charles Rudick, David Klumpp, and Anthony Schaeffer Praveen ThumbikatPraveen Thumbikat More articles by this author , Charles RudickCharles Rudick More articles by this author , David KlumppDavid Klumpp More articles by this author , and Anthony SchaefferAnthony Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1478AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pain is the hallmark of patients with chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). The etiology and pathogenesis of this disease syndrome remains unknown. We hypothesized that mast cells and factors released by activated mast cells contribute to the pathogenesis of CPPS. We therefore examined clinical samples from CPPS patients for mast cell activation products. Mechanisms of chronic pelvic pain were further defined in a murine experimental autoimmune prostatitis (EAP) model. METHODS Expressed prostatic secretions (EPS) from patients with CPPS were tested for the presence of mast cell degranulation products using substrate-based assays. Prostatitis was induced in wild type and mast cell deficient male mice using rat prostate antigen with adjuvant. Mice were tested prior to antigen injection (baseline) and at various times post-injection. Referred hyperalgesia and tactile allodynia were tested using von Frey filaments applied to the abdomen and the plantar region of the hind paw. Therapy was administered to mice with inhibitors of mast cell degranulation as well as functional inhibitors of mast cell activated factors. RESULTS Activated factors released by mast cells were significantly elevated in EPS from CPPS patients compared to controls. In the murine model of pelvic pain, increased recruitment and activation of mast cells was detected along with expression of nerve growth factor and enhanced neuronal density. In contrast, mast cell deficient mice demonstrated significantly attenuated pelvic pain. Finally, treatment of mice with inhibitors of mast cell degranulation as well as functional inhibitors of mast cell activated factors significantly attenuated pelvic pain behavior. CONCLUSIONS Our results demonstrate that mast cells and their activation products play an important role in the pathogenesis of chronic pelvic pain and may be involved in pain mechanisms in CP/CPPS. Furthermore, therapies targeting mast cell activation appear to be efficacious in reducing established pelvic pain in animal models. Chicago, IL© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e313 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Praveen Thumbikat More articles by this author Charles Rudick More articles by this author David Klumpp More articles by this author Anthony Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...