Treatment options for the overactive bladder were recently discussed at the 4th International Consultation on Incontinence (ICI) held in Paris, 5-8 July 2008. This article will overview current thoughts on the pharmacological and clinical basis for the different classes of drugs currently used for the treatment of lower urinary tract symptoms/overactive bladder syndrome/and detrusor overactivity. Individual drugs are not discussed in detail; particular consideration is given to therapeutic aspects of the management of the elderly patient. An extensive literature review confirms the rationale for using antimuscarinic drugs, and that the currently used drugs are efficacius with an acceptable tolerability and safety. In patients resistant to antimuscarinics, botulinum toxin may be an alternative--the vanilloids resiniferatoxin and capsaicin have very limited use. New therapeutic options with positive proof-of-concept studies, but with limited clinical experience, are beta3 adrenoceptor agonists and phosphodiesterase type 5 inhibitors. Positive signals have been found for other classes of drugs (e.g., gonadotropin-releasing hormone antagonists, neurokinin receptor-1 antagonists), but available information is not sufficient for proper assessment. Antimuscarinic drugs remain the first-line treatment of the overactive bladder and a favorable efficacy/tolerability-safety ratio can be confirmed. Promising new alternatives are emerging and future controlled studies will decide their place in the therapeutic arsenal.

The bladder mucosa consists of the urothelium, basement membrane, and lamina propria (LP). Although the urothelium has been given much attention, it may be regarded as one part of a signaling system involving another equally important component of the bladder mucosa, namely, the LP. The LP lies between the basement membrane of the mucosa and the detrusor muscle and is composed of an extracellular matrix containing several types of cells, including fibroblasts, adipocytes, interstitial cells, and afferent and efferent nerve endings. In addition, the LP contains a rich vascular network, lymphatic vessels, elastic fibers, and smooth muscle fascicles (muscularis mucosae). The roles of the LP and its components in bladder function have not been definitively established, though it has been suggested to be the capacitance layer of the bladder, determining bladder compliance and enabling adaptive changes to increasing volumes. However, the bladder LP may also serve as a communication center, with an important integrative role in signal transduction to the central nervous system (nociception, mechanosensation). The LP may also, by means of its different components, make it possible for the urothelium to transmit information to other components of the bladder wall, contributing to activation of the detrusor muscle. In addition, the LP may serve as a source for production of factors influencing the growth of both the overlying urothelium and the underlying detrusor muscle. Neurourol. Urodynam. 33:9–16, 2014. © 2013 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.