Lower urinary tract dysfunction: From basic science to clinical management

Authors


This special issue of International Journal of Urology contains six invited review articles that focus primarily on the contribution of sensory mechanisms to lower urinary tract (LUT) dysfunction and the mechanisms by which different therapies reduce LUT symptoms by targeting sensory pathways. While antimuscarinic drugs, which reduce motor activity of the bladder by blocking post-junctional muscarinic receptors, are still the primary treatment for overactive bladder and urinary incontinence, there has been increasing interest in the contribution of sensory mechanisms to LUT dysfunction and in therapies to normalize sensory pathways. Abnormal activity in peripheral afferent nerves or abnormal processing of that activity in the central nervous system can trigger irritative bladder symptoms (urgency, frequency), as well as involuntary bladder contractions leading to urinary incontinence. Thus, therapies that reduce the afferent limb of the micturition reflex could reduce all of the major symptoms of overactive bladder. It is known that bladder afferents can respond to mechanical, as well as chemical stimuli by expressing a variety of receptors and ion channels. Pathological conditions can affect the excitability of afferents by altering the expression and/or properties of these receptors/channels, and in turn alter LUT function. Afferent activity can also be altered indirectly by conditions that affect the urothelium, which not only functions as a protective barrier, but can also respond like afferent nerves to mechanical and chemical stimuli, and release chemicals that influence the properties of adjacent afferent nerves. Thus, afferent mechanisms in the LUT are complex and susceptible to a variety of stimuli.

This special issue begins with a review by Birder of the properties of bladder afferent nerves and urothelium, and the chemical signaling between these two cell types that might underlie LUT dysfunction. The second paper by Cho and Kim focuses on biomarkers present in the urine, bladder or serum that are associated with LUT symptoms. Many of these biomarkers, such as nerve growth factor, prostaglandins and cytokines, are known to to be released by urothelial cells and to act on afferent nerves. Therefore, they might play a role in urothelial-afferent signaling and in the generation of abnormal afferent activity underlying LUT dysfunction. The third paper by Hood and Andersson summarizes the data suggesting that three different therapies; mirabegron (a beta-3 adrenergic receptor agonist), tadalafil (a PDE-5 inhibitor) and botulinum toxin, which are effective in reducing LUT symptoms, can target afferent nerves in the bladder in addition to influencing other cell types, such as urothelial cells and smooth muscle. The fourth paper by Yamaguchi reviews the actions of various drugs used to treat LUT dysfunction. The fifth paper by Kuo and Kuo discusses the uses, mechanisms of action and methods of administration of botulinum toxin type A to the urinary bladder and or urethra/prostate for treatment of neurogenic and non-neurogenic LUT dysfunctions. The possible effects of the toxin on afferent nerves and/or urothelial cells is discussed. The sixth paper by Yoshimura et al. discusses experimental studies in animals in which various gene therapy methods were used to modulate the functions of trophic factors, neurotransmitters, cytokines and ion channels in the bladder and in bladder neural pathways. Much of this review focuses on therapies targeting afferent systems.

In summary, this special issue of the journal prepared by experts in the field of neurourology represents a comprehensive summary of current knowledge related to the pathophysiology of afferent mechanisms in the LUT and therapies used to treat overactive bladder that might act in part by targeting these mechanisms.

Conflict of interest

None declared.

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