Experimental autoimmune prostatitis induces microglial activationinthe spinal cord

Larry Wong, Joseph D. Done, Anthony J. Schaeffer, Praveen Thumbikat*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

BACKGROUND. The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain.

METHODS. Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S14-S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain.

RESULTS. Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1b, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1b, P2X4R, and BDNF. CONCLUSION. Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain.

Original languageEnglish (US)
Pages (from-to)50-59
Number of pages10
JournalProstate
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • CPPS
  • Microglia
  • Neuroinflammation
  • Pelvic pain
  • Prostatitis

ASJC Scopus subject areas

  • Oncology
  • Urology

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