Latest insights into the pathophysiology of bladder pain syndrome/interstitial cystitis.

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common medical problem in both sexes affecting people of all ages. Patients might report overactive bladder symptoms with additional bladder pain at maximum bladder filling, during and after micturition. This review aims to highlight pathophysiological mechanisms associated with this disease. RECENT FINDINGS: Latest literature exposes different pathophysiological mechanisms such as impaired urothelial barrier function, alteration of urothelial factors and cytokines, chronic inflammation, vascular lesions, neurogenic inflammation and processes in the central nervous system leading to central sensitization. According to the involved mechanisms, BPS/IC may be arranged in clusters according to the clinical phenotype thus helping in clinical decision-making and treatment. Moreover, patients with BPS/IC suffer from other comorbidities such as fibromyalgia, irritable bowel syndrome, chronic pain and functional syndromes and psychosomatic diseases making the management challenging for medical professionals. SUMMARY: Bladder pain syndrome/interstitial cystitis is a complex heterogeneous medical condition involving different pathomechanisms leading to bladder pain and dysfunction, consequently, impairing quality-of-life in affected individuals. However, these mechanisms are still not fully understood, so that patient treatments often remain unsatisfactory. For this reason, continuing research is important to understand the underlying pathomechanisms to discover biomarkers and treatment targets eventually improving diagnostic and therapeutic measures of BPS/IC.

Sacral Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction.

BACKGROUND: Neurogenic lower urinary tract dysfunction (NLUTD) is a highly prevalent and disabling condition; nevertheless, standard treatments often remain unsatisfactory. Sacral neuromodulation (SNM) is a well-established therapy for non-NLUTD, but there is a lack of randomized controlled trials to show benefit in patients with NLUTD. METHODS: For this sham-controlled, double-blind, multicenter trial, patients with refractory NLUTD (and intended SNM) were recruited at four Swiss SNM referral centers. After lead placement into the sacral foramina S3 (rarely, S4), all participants underwent SNM testing. If successful (≥50% improvement in key bladder diary variables), the neurostimulator was implanted for permanent stimulation. For 2 months, neuromodulation was optimized using subsensory stimulation with individually adjusted parameters. Thereafter, the neurostimulator remained on or was switched off (1:1 random allocation to group SNM ON or SNM OFF, respectively) for 2 months, followed by a neurourologic reevaluation. The primary outcome was success, as defined above, of SNM compared with baseline. RESULTS: Of 124 patients undergoing SNM testing, 65 (52%) had successfully improved lower urinary tract function. Of these, 60 patients (median age, 49.5 years; 43 women) were randomly assigned to the intervention. After 2 months of intervention, the SNM ON group demonstrated a success rate of 76%. In the SNM OFF group, 42% of patients showed sustained SNM effects despite their neurostimulator being switched off during the last 2 months (odds ratio, 4.35; 95% confidence interval, 1.43 to 13.21; P=0.009). During the entire study period, there were 11 adverse events (6 dropouts; no dropouts during the intervention phase). CONCLUSIONS: SNM effectively corrected refractory NLUTD in the short term in well-selected neurologic patients. (Funded by the Swiss National Science Foundation, Vontobel­Stiftung, Gottfried und Julia Bangerter­Rhyner Stiftung, Dr. Urs Mühlebach, and the Swiss Continence Foundation; ClinicalTrials.gov number, NCT02165774.)