Role of gram‐positive bacteria in chronic pelvic pain syndrome (CPPS)

• Published in: The Prostate Vol. 79; no. 2; pp. 160 - 167
• Main Authors: Murphy, Stephen F., Anker, Jonathan F., Mazur, Daniel J., Hall, Christel, Schaeffer, Anthony J., Thumbikat, Praveen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2019
• Subjects: Animals; Bacteria; Chronic Pain - immunology; Chronic Pain - microbiology; Colonization; CPPS; Etiology; Flow cytometry; Gram-negative bacteria; Gram-Positive Bacteria - isolation & purification; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections - microbiology; gram‐positive; Humans; Hyperalgesia - microbiology; Immune response; infection; Inoculation; Lymph Nodes - immunology; Lymph Nodes - microbiology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Monocytes; Pain; Pain perception; Patients; Pelvic Pain - immunology; Pelvic Pain - microbiology; Prostate; Prostate - immunology; Prostate - microbiology; prostatitis; Prostatitis - microbiology; Random Allocation; Retrospective Studies; Staphylococcus epidermidis; Strains (organisms); T-Lymphocytes - immunology; Tactile stimuli; Urethral Diseases - immunology; Urethral Diseases - microbiology; Urine; infection; pain; prostatitis; gram-positive; CPPS
• ISSN: 0270-4137; 1097-0045; 1097-0045
• DOI: 10.1002/pros.23721

INTRODUCTION Chronic pelvic pain syndrome (CPPS) is a complex disorder that affects a large proportion of all men. A limited understanding of its etiology and pathogenesis is reflected by the absence of effective therapies. Although CPPS is deemed clinically non‐infectious with no well‐defined etiological role for microbes, bacteria is readily isolated from both healthy and patient prostate secretion and urine samples. Our laboratory has previously demonstrated that a specific gram‐negative bacterial isolate can induce CPPS‐like symptoms in mice. Here we aimed to expand on these findings examining the role of gram‐positive patient‐derived bacteria in CPPS. METHODS A retrospective analysis of bacterial cultures from CPPS patients from a single center was performed. Gram‐positive bacteria were isolated from the expressed prostatic secretion (EPS) of three CPPS‐patients (pain inducers, PI) and one from a healthy volunteer (non‐pain inducer, NPI). These bacteria were inoculated intra‐urethrally in two mouse backgrounds and analyzed for their ability to induce tactile allodynia, voiding dysfunction, and colonize the murine prostate. Host immune responses to bacterial instillation were analyzed by flow cytometry. RESULTS PI strains (Staphylococcus haemolyticus 2551, Enterococcus faecalis 427, and Staphylococcus epidermidis 7244) induced and maintained tactile allodynia responses (200% increase above baseline) for 28 days in NOD/ShiLtJ mice. Conversely the healthy subject derived strain (Staphylococcus epidermidis NPI) demonstrated no significant pelvic allodynia induction. Intra‐urethral inoculation of the four bacterial strains into C57BL/6 mice did not induce significant increases in pain responses. Infected NOD/ShiLtJ displayed significant voiding dysfunction compared to their control counterparts. Colony counts of prostate tissues from both NOD/ShiLtJ and C57BL/6 mice at day 28 demonstrated that bacterial strains colonized equally well, including NPI. We also determined that mechanistically, the patient‐isolates induced prostate inflammation specifically involving T‐cells and monocytes. CONCLUSIONS Gram‐positive isolates from CPPS patients showed enhanced ability to induce tactile allodynia compared to a single taxonomically similar gram‐positive strain isolated from a healthy control. Responses were shown to be dependent on host genetic background and not on colonization differences between strains.