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Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives
- Source :
- International Neurourology Journal, Vol 28, Iss Suppl 1, Pp S2-33 (2024)
- Publication Year :
- 2024
- Publisher :
- Korean Continence Society, 2024.
-
Abstract
- Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. Also, a series of local signals called autonomous myogenic contraction, micromotion, or afferent noises, which can occur during bladder filling, may be induced by the leak of acetylcholine (ACh) or urothelial release of adenosine triphosphate (ATP). They can be transmitted to the central nervous system through afferent fibers to trigger coordinated urgency-related detrusor contractions. Antimuscarinics, commonly known to induce smooth muscle relaxation by competitive blockage of muscarinic receptors in the parasympathetic postganglionic nerve, have a minimal effect on detrusor contraction within therapeutic doses. In fact, they have a predominant role in preventing signals in the afferent nerve transmission process. β3-adrenergic receptor (AR) agonists inhibit afferent signals by predominant inhibition of mechanosensitive Aδ-fibers in the normal bladder. However, in pathologic conditions such as spinal cord injury, it seems to inhibit capsaicin-sensitive C-fibers. Particularly, mirabegron, a β3-agonist, prevents ACh release in the BOO-induced detrusor overactivity model by parasympathetic prejunctional mechanisms. A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial β3-AR.
Details
- Language :
- English
- ISSN :
- 20934777 and 20936931
- Volume :
- 28
- Issue :
- Suppl 1
- Database :
- Directory of Open Access Journals
- Journal :
- International Neurourology Journal
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.751d7b1fb20043b58a553379a6f14cd9
- Document Type :
- article
- Full Text :
- https://doi.org/10.5213/inj.2448002.001