Mast Cell-Derived Histamine Mediates Cystitis Pain

Background: Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC) is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC. Methods and Findings: Infection of mice with pseudorabies virus (PRV) induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF), TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology. Conclusions: These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, an

The role of PCA3 testing in patients with a raised prostate-specific antigen level after Greenlight photoselective vaporization of the prostate

Background and Purpose: Greenlight® photoselective vaporization of the prostate (PVP) is an effective method for treating men with lower urinary tract symptoms. A rise in prostate specific antigen (PSA) levels, however, may be noticed in some patients during follow-up. The aim of this study was to determine whether the prostate cancer gene 3 (PCA3) urinary test would help identify patients who were in need of a prostate biopsy. Patients and Methods: The PSA of all patients undergoing PVP were analyzed. Patients with an elevated (above reference range) or rising PSA level (defined as >0.75 ng/mL/year if the PSA was between 4.1 and 10 or a doubling time of less than 2 years) were offered a transrectal ultrasonography (TRUS) guided prostate biopsy. Before the biopsy procedure, all patients had a PCA3 test. The relationships between PSA, PCA3, and TRUS prostate biopsy findings were analyzed to determine sensitivity and specificity for the PCA3 test in this setting. Results: 50 patients were identified. The mean age was 69.97 (range 57–83) years. The mean PSA level was 10.1 ng/mL (range 3.03–44.2 ng/mL). Six patients were found to have prostate cancer. Of those, five patients had a positive PCA3 test. One patient had a negative PCA3 test but positive biopsy findings. This gives a sensitivity of 83.3%, and a positive predictive value of 21.7%. The negative predictive value was 96%. Conclusion: The results suggest that a negative PCA3 test in our group of patients is a good predictor of negative biopsy results. The low positive predictive value may be an artefact of the group size. This will need further investigation and greater patient numbers to determine