title: Chronic Prostatitis Induces Bladder Hypersensitivity and Sensitizes Bladder Afferents in the Mouse.
abstract: OBJECTIVE
  Chronic prostatitis/chronic pelvic pain syndrome causes symptoms that include the frequent and urgent need to urinate, pain or burning during urination and pain radiating to the back, abdomen and/or colorectum. These bladder symptoms suggest that chronic prostatitis/chronic pelvic pain syndrome 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 the prostate and bladder after inflammation of the prostate and 2) bladder function and bladder afferent sensitization.
  
  
  METHODS
  Prostate and bladder histology, immunohistochemistry and expression of immunomodulatory targets were examined weekly after zymosan or vehicle was injected in the dorsal lobe of the mouse prostate. Cystometry, bladder and bladder afferent sensitivity were also assessed weekly.
  
  
  RESULTS
  Prostate inflammation induced significant up-regulation in proinflammatory and anti-inflammatory cytokines TNF-α (tumor necrosis factor-α) and IL-10 (interleukin-10), growth factor NGF (nerve growth factor), and T-lymphocyte markers FoxP3, CD4 and CD8 in the prostate and the 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 retrograde tracers DiI and Fast Blue in the bladder wall and the prostate, respectively. This showed that a significant proportion (approximately 17%) of dorsal root ganglion afferent somata contained tracers from the bladder and the prostate.
  
  
  CONCLUSIONS
  These observations support an afferent contribution to chronic prostatitis/chronic pelvic pain syndrome and cross-organ sensitization from prostate to bladder.
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: ericaschwartz79@gmail.com.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Schwartz
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: La
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Young
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sonali
authors.initials: S
authors.lastname: Joyce
authors.affiliation: Center for Pain Research, Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011472:Prostatitis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D012313:RNA / Q000235:genetics; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000294:innervation*; D001745:Urinary Bladder Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics
chemical_list: D016207:Cytokines; D012313:RNA
keywords: bladder; pain; prostate; prostatitis; visceral afferents