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Clinically isolated gram-positive prostate bacteria induce chronic pelvic pain.

Login to Access Video or Poster Abstract: MP11-07
Sources of Funding: NIH R01DK094898, R01DK108127.

Introduction

Gram-positive bacterial strains comprise the most common isolates found in both healthy and CPPS patient samples. The role of these bacteria in development and maintenance of pain in CPPS is unknown

Methods

Gram-positive bacteria were isolated from the prostates, i. e. bacteria count was 1 log greater in the EPS or VB3 than that in the VB1 and VB2, of three CPPS patients (pain inducers, PI) and one from a healthy volunteer (non-pain inducer, NPI). The bacteria were inoculated intra-urethrally in two genetic mouse backgrounds and analyzed for their ability to induce tactile allodynia and to colonize the murine prostate.

Results

PI strains (Staphylococcus haemolyticus 2551, Enterococcus faecalis 427 and Staphylococcus epidermidis 7244) were capable of inducing and maintaining robust tactile allodynia responses (200% increase above baseline) for 28 days initiating at day 7 post-infection in NOD/ShiLtJ mice. Conversely the healthy subject derived strain (Staphylococcus epidermidis NPI) demonstrated no significant pain responses above baseline at any time-point examined (Days 7, 14, 21, 28). Intra-urethral inoculation of any of the four bacterial strains into C57BL/6 mice did not induce significant increases in pain responses above baseline. In vitro adherence and invasion assays revealed no significant difference between strains to invade WPMY or RWPE-1 cells. E. faecalis 427 demonstrated a reduced capacity for intracellular proliferation in WPMY but not RWPE-1 cells compared to the other strains. In vivo, colony counts were also performed on prostate tissues removed from both NOD/ShiLtJ and C57BL/6 mice at day 28 post-infection. All bacterial strains colonized equally well comparing within mouse background including NPI. Significant differences were observed however when comparing the bacterial loads of NOD/ShiLtJ and C57BL/6 mice.

Conclusions

Gram-positive isolates from the prostates of CPPS patients showed dramatically enhanced ability to induce tactile allodynia compared to taxonomically similar gram-positive strain isolated from a healthy control subject. Pain responses were shown to be dependent on the genetic background of the host and not on in vivo colonization differences between strains. All four strains demonstrated similar growth, invasion and proliferation responses in vitro, strongly implicating host:pathogen interactions in development of pain.

Funding

NIH R01DK094898, R01DK108127.

Authors
Stephen Murphy
Jonathan Anker
Anthony Schaeffer
Praveen Thumbikat
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