Role of Mast Cells in Male Chronic Pelvic Pain

Abstract

Chronic pelvic pain syndrome accounts for 90% of all chronic prostatitis but it has an unknown pathogenesis. We sought to understand the role of mast cells and nerve growth factor in chronic pelvic pain. Expressed prostatic secretions in men with chronic pelvic pain syndrome and controls were tested for mast cell tryptase and nerve growth factor. Mast cell number, activation status and nerve growth factor expression were examined in the NOD/ShiLtJ experimental autoimmune prostatitis model and in mast cell deficient KitW-sh/KitW-sh mice. Tactile allodynia was quantified using von Frey filaments as a measure of pelvic pain behavior. Inhibitors of mast cell degranulation, histamine receptor antagonists and anti-nerve growth factor neutralizing antibodies were tested to decrease pelvic pain behavior. Men with chronic pelvic pain syndrome showed increased mast cell tryptase and nerve growth factor in expressed prostatic secretions. In the experimental autoimmune prostatitis model increased total and activated mast cells were observed in the prostate. Mast cell deficient KitW-sh/KitW-sh mice showed attenuated pelvic pain behavior but no difference in inflammatory infiltrates in the prostate from controls. Mice with experimental autoimmune prostatitis also demonstrated increased intraprostatic nerve growth factor compared to that of KitW-sh/KitW-sh mice. Treatment of experimental autoimmune prostatitis with a mast cell stabilizer combined with a histamine 1 receptor antagonist resulted in a synergistic decrease in chronic pelvic pain. In contrast, neutralization of nerve growth factor in vivo did not result in pain relief. Results suggest that mast cells are important mediators of chronic pelvic pain in experimental autoimmune prostatitis cases. They may be potential targets for therapeutic intervention in men with chronic prostatitis/chronic pelvic pain syndrome.