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Context Detrusor underactivity (DUA) is a common but relatively under-researched bladder dysfunction. Underactive bladder (UAB) is the symptom-based correlate of DUA. Recently, there has been renewed interest in this topic. Objective To systematically review and summarise the most recent literature and discuss this in the context of what is already known. Evidence acquisition A systematic review of the literature was performed in December 2017 using Medline and Scopus databases. Separate searches of each database used a complex search strategy including “free text” protocols. Search terms included “underactive bladder”, “detrusor underactivity”, “acontractile bladder”, “detrusor failure”, “detrusor areflexia”, “atonic bladder”, “chronic retention”, and “impaired bladder contractility”. Evidence synthesis The initial search retrieved a total of 1690 studies; of these 44 were included in the final analyses. Conclusions Although there has been an expansion in the literature concerning all aspects of DUA and UAB, knowledge on its epidemiology and aetiopathogenesis is still lacking; there remains a need to develop accurate reproducible diagnostic criteria and effective treatments, in particular drug therapies. Patient summary Recently, there has been renewed interest in underactive bladder with expanding research in this area. The lack of simple, reproducible, noninvasive diagnostic criteria has precluded an accurate estimation of the magnitude of the problem. Recent studies have highlighted the potential role of impaired bladder blood supply in causing bladder underactivity.

BACKGROUND: Improvement of bladder emptying by modulating afferent nerve activity is an attractive therapeutic strategy for detrusor underactivity. Transient receptor potential vanilloid 4 (TRPV4) is a sensory ion channel in urothelial cells that contribute to the detection of bladder filling. OBJECTIVE: To investigate the potential benefit of intravesical TRPV4 agonists in a pelvic nerve injury rat model for detrusor underactivity. DESIGN, SETTING, AND PARTICIPANTS: Female wild-type and Trpv4 knockout rats underwent sham surgery or bilateral pelvic nerve injury (bPNI). Four weeks later, rats underwent cystometry with infusion of the TRPV4 agonist GSK1016790A. Bladders were harvested for in vitro pharmacological studies, quantitative reverse polymerase chain reaction and immunohistochemistry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data are expressed as median ± interquartile range. Statistical comparisons were made using the Mann-Witney U test and Wilcoxon signed rank test as appropriate. RESULTS AND LIMITATIONS: Rats with bPNI showed a phenotype characteristic of detrusor underactivity with lower-amplitude voiding contractions, decreased voiding frequency, and increased postvoid residual. Intravesical application of GSK1016790A increased voiding frequency and reduced postvoid residual in wild-type, but not Trpv4-/-, rats. In isolated bladder strips, GSK1016790A did not induce relevant contractions, indicating that the observed improvements in bladder function are the result of increased afferent signalling through TRPV4 activation, rather than a local effect on the detrusor. The altered urinary phenotype of Trpv4-/- mice was not apparent in the Trpv4-/- rat model, suggesting species-related functional variations. Our results are limited to the preclinical setting in rodents. CONCLUSIONS: Intravesical activation of TRPV4 improves bladder dysfunction after bPNI by increasing afferent signalling. PATIENT SUMMARY: We demonstrate that the sensory protein transient receptor potential vanilloid 4 (TRPV4) can be targeted to improve bladder function in animals that have iatrogenic injury to the nerves innervating the bladder. Further research is required to determine whether these results can be translated to patients with an underactive bladder. ispartof: EUROPEAN UROLOGY vol:74 issue:3 pages:336-345 ispartof: location:Switzerland status: published