Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

International Neurourology Journal, 2024 · DOI: 10.5213/inj.2448002.001 · Published: February 29, 2024

Simple Explanation

Overactive bladder (OAB) is defined by urinary urgency, frequency, and nocturia. The causes can be bladder outlet obstruction, aging, psychological stress and more. Several mechanisms contribute to OAB, including neurogenic, myogenic, and urothelial factors. Antimuscarinics, which relax smooth muscles, mainly prevent afferent nerve transmission. β3-adrenergic receptor (AR) agonists inhibit afferent signals, with mirabegron preventing acetylcholine release in bladder outlet obstruction models. Vibegron has dual action: inhibiting acetylcholine from cholinergic efferent nerves and afferent inhibition via urothelial β3-AR. The review summarizes OAB pathophysiology, treatments, and β3-AR mechanisms under various conditions.

Study Duration

Not specified

Participants

Animal models and human studies reviewed

Evidence Level

Review Article

Key Findings

1
OAB pathophysiology involves neurogenic, myogenic, and urothelial mechanisms, with afferent noises triggering urgency-related detrusor contractions.
2
Antimuscarinics primarily affect afferent nerve transmission, while β3-AR agonists inhibit mechanosensitive Aδ-fibers in normal bladders and capsaicin-sensitive C-fibers in spinal cord injury.
3
Mirabegron prevents ACh release in BOO-induced detrusor overactivity. Vibegron inhibits ACh from cholinergic efferent nerves and afferent inhibition via urothelial β3-AR.

Research Summary

This review article explores the pathophysiology of overactive bladder (OAB), highlighting the neurogenic, myogenic, and urothelial mechanisms involved in its development. It discusses how afferent signals and neurotransmitters play a crucial role in triggering bladder contractions and urgency. The article examines the pharmacological treatments for OAB, including antimuscarinics, β3-adrenergic receptor agonists, and botulinum toxin A. It explains their mechanisms of action, particularly focusing on how β3-AR agonists like mirabegron and vibegron inhibit afferent signals and modulate cholinergic transmission. The review also delves into the role of various pathological conditions such as bladder outlet obstruction, bladder ischemia, metabolic syndrome, psychological stress, urinary microbiome, and inflammation in the etiology of OAB. It emphasizes the potential for pathogenesis-oriented therapy for OAB patients who do not respond to conventional treatments.

Practical Implications

Personalized Treatment Strategies

Understanding the diverse etiologies and mechanisms of OAB can lead to tailored treatment approaches based on individual patient profiles.

Targeted Drug Development

Further research into the specific action mechanisms of drugs like β3-AR agonists can result in more effective and targeted therapies with fewer side effects.

Holistic Management of OAB

Addressing underlying conditions such as metabolic syndrome, psychological stress, and inflammation may improve OAB symptoms and overall patient outcomes.

Study Limitations

1
Animal models may not perfectly represent all clinical pathologies of OAB.
2
The exact mechanisms of action for some OAB medications are still not fully understood.
3
Phenotype standardization for OAB is lacking, making it difficult to compare treatment outcomes across different patient populations.

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