Pathophysiological Mechanisms Involved in Overactive Bladder/Detrusor Overactivity

Abstract

Purpose of Review To examine the latest published findings on the pathophysiological mechanisms involved in the development of overactive bladder (OAB) and detrusor overactivity (DO), and to identify common pathways linked to the risk factors associated with these conditions. Recent Findings Evidence is accumulating, both clinical and experimental, that many of the factors linked to the development of OAB/DO, including ageing, bladder outlet obstruction, psychological stress, and obesity are associated with reduced bladder blood flow. This induces local tissue inflammation with cytokine release and enhanced oxidative stress, ultimately resulting in altered detrusor sensitivity, detrusor hypertrophy and fibrosis, together with afferent hypersensitivity. These mechanisms would explain the symptoms of urgency and frequency observed in OAB patients. Although not a characteristic of OAB, undetected low level bacterial infections of the bladder have been proposed to explain the OAB symptoms in patients resistant to standard treatments. In this condition, inflammatory responses without reductions in perfusion activate the inflammatory pathways. Summary Evidence is mounting that poor bladder perfusion and local inflammatory responses are central mechanisms involved in the development of OAB/DO. As our understanding of these pathophysiological mechanisms advances, new avenues for drug development will be identified and ultimately treatment may become more individualized depending on the particular pathway involved and the drugs available.

Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? : Research on the events in smooth muscle, collagen, interstitial cell and telocyte expression

“…These changes were observed starting from 4 weeks and progressing through 8 weeks, and up to 16 weeks, respectively. 7,[10][11][12][13] Morphological changes in OAB in these animal models showed an increased amount of collagen tissue, changes in smooth muscles, and an increased thickness of the bladder wall. It has been suggested that the increased connective tissue in OAB may play a relevant role in achieving normal bladder function.…”

Can apparently transient life events trigger long‐term lower urinary tract symptoms?

“…Corticotropin releasing hormone has been implicated in some these associations with links to depression, anxiety and LUTS. 15,16 Use of the antagonist astressin has been shown to block some of these responses in rats. 16 Severe traumatic life events can also result in changes to the gray matter in the brain.…”

“…These central transmission pathways are also linked in the development of post‐traumatic stress disorder. Corticotropin releasing hormone has been implicated in some these associations with links to depression, anxiety and LUTS 15,16 . Use of the antagonist astressin has been shown to block some of these responses in rats 16 .…”

Could a better understanding of the underlying pathophysiologies lead to more informed treatment choices in patients with lower urinary tract dysfunction due to an acontractile or underactive detrusor? ICI‐RS 2023

“…The association might involve corticotropin releasing factor. 16 Adverse childhood experiences and stress can result in a cascade of pro-inflammatory cytokines and chemokines at the central as well as peripheral level resulting in altered lower urinary tract function. Voiding abnormalities have been shown to occur including underactivity.…”

“…Voiding abnormalities have been shown to occur including underactivity. [16][17][18] Mental health problems can impact several areas of the brain that are associated with voiding function including the hypothalamus, amygdala, insula with projections to the pontine micturition center. These key areas of the limbic system involved with emotion send neuronal inputs to the micturition center and might explain this association.…”