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Aims The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. Methods This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. Results Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. Conclusions This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disorder that is characterized by persistent pelvic pain in men of any age. Although several studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel is involved in various pathways of chronic pain, the TRPV1 channel has not been implicated in chronic pelvic pain associated with CP/CPPS. Methods Male C57BL/6J (B6) and TRPV1 knockout (TRPV1 KO) mice (5-7 weeks old) were used to study the development of pelvic allodynia in a murine model of CP/CPPS called experimental autoimmune prostatitis (EAP). The prostate lobes, dorsal root ganglia (DRG), and spinal cord were excised at day 20. The prostate lobes were assessed for inflammation, TRPV1 expression, and mast cell activity. DRG and spinal cord, between the L6-S4 regions, were analyzed to determine the levels of phosphorylated ERK1/2 (p-ERK 1/2). To examine the therapeutic potential of TRPV1, B6 mice with EAP received intraurethral infusion of a TRPV1 antagonist at day 20 (repeated every 2 days) and pelvic pain was evaluated at days 20, 25, 30, and 35. Results Our data showed that B6 mice with EAP developed pelvic tactile allodynia at days 7, 14, and 20. In contrast, TRPV1 KO mice with EAP do not develop pelvic tactile allodynia at any time point. Although we observed no change in the levels of TRPV1 protein expression in the prostate from B6 mice with EAP, there was evidence of significant inflammation and elevated mast cell activation. Interestingly, the prostate from TRPV1 KO mice with EAP showed a lack of mast cell activation despite evidence of prostate inflammation. Next, we observed a significant increase of p-ERK1/2 in the DRG and spinal cord from B6 mice with EAP; however, p-ERK1/2 expression was unaltered in TRPV1 KO mice with EAP. Finally, we confirmed that intraurethral administration of a TRPV1 antagonist peptide reduced pelvic tactile allodynia in B6 mice with EAP after day 20. Conclusions We demonstrated that in a murine model of CP/CPPS, the TRPV1 channel is key to persistent pelvic tactile allodynia and blocking TRPV1 in the prostate may be a promising strategy to quell chronic pelvic pain.

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression.

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-1β, 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-1β, 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. Prostate 75:50–59, 2015. © 2014 Wiley Periodicals, Inc.

Peyronie disease (PD) arises from the deposition of collagen and fibrin that creates a plaque in the tunica albuginea of the penis. The resulting induration and curvature of the penis leads to sexual dysfunction in many men. Despite the prevalence of the disease and natural history studies that suggest progression, men might not seek therapeutic intervention due to a lack of general knowledge about the disease, its pathophysiology, and treatments aimed at ameliorating its symptoms. Medical therapy using oral, topical, or intralesionally delivered drug is pursued in all but the most severe cases. This review of the literature in the last 4 years attempts to identify new trials of therapies and treatment modalities aimed at altering the PD process. Specifically, we will address clinical trials evaluating oral pharmacotherapies; topical, intralesional, and shockwave therapies; and penile traction devices. We will discuss the level of evidence and support for each of the new clinical trials.

A case of clear cell adenocarcinoma arising in the female urethra is described. The tumor had a tubulocystic pattern and intracytoplasmic glycogen, resembling clear cell carcinomas that occur in the vagina and upper female genital tract. Ultrastructural study, however, showed abundant and elongated microvilli on the tumor cells, a feature not seen in clear cell carcinomas or other common forms of carcinoma arising in the female genital tract. Six other cases of similar tumors of the female urethra were found in medical literature, yet there was no example of this tumor in the bladder or male urethra. Clinical and ultrastructural observations suggest that clear cell carcinoma of the female urethra is a distinctive neoplasm. Abundant microvilli provide morphologic evidence supporting the possibility of origin from the mesonephros. Radical extirpative surgery with urinary diversion appears to be the treatment of choice.

A dosimetry study of factors affecting the extent of tissue damage inflicted upon the canine renal cortex by the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser was undertaken. Laser parameters and renal tissue conditions were varied independently in duplicate in the following manner: (1) power - 5, 10, 20, 50, 75, 100 watts with a spot size of 1.2 mm; (2) exposure duration - 1, 2, and 4 seconds; (3) kidney perfusion and temperature--renal artery unclamped (perfused) without cooling; renal artery clamped (non-perfused) without cooling; and renal artery clamped with cooling. Five days following application of the laser, the animals were sacrificed and serial sections of the renal cortex were examined for maximum depth and width of tissue damage and ablation. Multiple linear regression analysis of the data indicated a direct linear relationship between the joules (watts X seconds) of energy delivered to the renal cortex and the depth and width of tissue damage and ablation (p less than 0.001 for joule regression coefficient for each variable). Seconds and/or watts alone were not major predictors of the outcome after accounting for joules. Clamping the main renal artery significantly reduced the depth and width of laser damage when compared to the perfused kidney (p less than 0.001 for each variable). The depth of damage was similar in the cooled and the non-cooled non-perfused kidney. These data suggest that increased laser energy and kidney perfusion significantly increase renal cortical laser induced damage. Adjustment of these parameters may permit controlled tumor ablation or tissue incision with minimal damage to adjacent normal tissue.

Inoculation of Escherichia coli into the ventral lobe of the rat prostate produced positive bacterial cultures in the expressed fluid of all three lobes of the rat prostate for a prolonged period of time. Orchiectomy at the time of bacterial inoculation significantly shortened the interval of positive bacterial cultures in the prostate expressate.