Different anatomical origins of urgency have been proposed with historically two hypotheses, the myogenic (urgency initiated from the detrusor muscle) and the neurogenic (urgency initiated from the central nervous system (CNS)). The increasing evidence regarding the role of urothelium/suburothelium and bladder afferent signaling has given birth to a third “urotheliogenic” hypothesis (urgency initiated from the urothelium/suburothelium). Despite less clearly established, a fourth anatomical generator of urgency, the urethra, has been patently evidenced with a noticeable refinement of its understanding and possible implication over the past decades (“urethrogenic” hypothesis). Finally, growing interest regarding underactive bladder and detrusor overactivity may be argued for a fifth mixed anatomical mechanism, from both a detrusor muscle and urothelium/suburothelium dysfunctions, as underactive bladder symptoms commonly overlap those of OAB (“urothelio-myogenic” hypothesis).
Several pathophysiological co-factors have been implied as possible important determinants in OAB pathogenesis. Increasing evidence over the past few years has shown that metabolic syndrome, affective disorders, central sensitization, sex hormones deficiency, urinary microbiota, gastrointestinal functional disorders, subclinical autonomic nervous system dysfunction, may favor OAB and that OAB could have its own specific pathophysiology in all of these frameworks.
![OAB.png](/images/OAB.png)
A “Prism” spectrum approach could help identify these various OAB pathophysiological features using thorough clinical examination, urodynamics and likely several additional testings in the near future such as urinary markers, functional brain imaging, autonomic nervous system testings, quantitative sensory testings, serum assessments of corticotropin-releasing factor, testosterone,….
There is probably not one “single” idiopathic OAB syndrome but rather numerous non-neurogenic OAB phenotypes based on underlying mechanisms and pathophysiological co-factors/co-morbidities supporting a paradigm shift in OAB towards treatment strategies tailored to individual patient characteristics. However, there seems to be currently a lack of consensual techniques for assessing the relevant pathophysiological features of OAB and future studies are needed in this field.
Likewise, we believe that forthcoming studies should assess the outcomes of the various OAB treatments available nowadays in each different OAB subpopulations because the outcomes of each treatment might rely mostly on disease features and patient’s profiles. Pharmacological companies may be less inclined to promote trials assessing the outcomes of drugs in subgroups of patients because it would divide the potential subsequent market without decreasing studies-related costs.
Hence, it behooves the urological community to promote such studies. Finally, from a public health standpoint, the cost-effectiveness of a tailored vs. a “one-size fits all” treatment approach is still elusive and should be taken into consideration.
![OAB_Pathophysiology.png](/images/OAB_Pathophysiology.png)
Written by: Benoit Peyronnet, MD, Department of Urology, New York University New York, New York
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