Chronic prostatitis induces urinary bladder hypersensitivity and sensitizes bladder afferents in the mouse

PURPOSE - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) causes symptoms that include frequent and urgent need to urinate, pain or burning during urination, and pain radiating to the back, abdomen and/or colorectum.

These urinary bladder symptoms suggest that CP/CPPS is associated with sensitization of adjacent organs, termed cross-organ sensitization. The objective of this study was to determine the extent of: 1] changes in immunomodulatory mediators in both the prostate and bladder after inflammation of the prostate and 2] bladder function and bladder afferent sensitization.

MATERIALS/METHODS - Prostate and bladder histology, immuno-histochemistry, and expression of immunomodulatory targets were examined weekly after either zymosan or vehicle was injected into the dorsal lobe of the mouse prostate. Cystometry, urinary bladder and bladder afferent sensitivity were also assessed weekly.

RESULTS - Prostate inflammation induced a significant upregulation in pro- and anti- inflammatory cytokines (TNF-α and IL-10), growth factor NGF and T-lymphocyte markers (FoxP3, CD4, CD8) in both prostate and bladder. Notably, prostatitis significantly increased urinary voiding frequency, induced hypersensitivity to bladder distension, and sensitized bladder afferents. We also examined sensory (afferent) co-innervation by injecting different retrograde tracers into the bladder wall (DiI) and prostate (fast blue, FB), finding that a significant proportion (∼ 17%) of dorsal root ganglion afferent somata contained tracers from both the bladder and prostate.

CONCLUSIONS - These observations support an afferent contribution to CP/CPPS and cross-organ sensitization from prostate to bladder.

The Journal of urology. 2016 Mar 17 [Epub ahead of print]

Erica S Schwartz, Jun-Ho La, Erin E Young, Bin Feng, Sonali Joyce, G F Gebhart

Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213. Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213., Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213., Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213., Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213., Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA 15213.

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