Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment.

Jia-Fong Jhang,Hann-Chorng Kuo,Yuan-Hong Jiang,Yu-Khun Lee

doi:10.3390/biomedicines10020396

Jia-Fong Jhang, Hann-Chorng Kuo + Show 2 more

Open Access

https://doi.org/10.3390/biomedicines10020396

Copy DOI

Journal: Biomedicines	Publication Date: Feb 7, 2022
Citations: 10	License type: CC BY 4.0

Affiliation: Tzu Chi University

Abstract

Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

Highlights

In our prospective, randomized controlled trials in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) refractory to treatment, we demonstrated that a suburothelial botulinum toxin A (BoNT-A) injection plus cystoscopic hydrodistention significantly improved visual analog scale (VAS) scores of bladder pain, functional and cystometric bladder capacity, and global response assessment at 3 months after treatment, when compared with patients receiving cystoscopic hydrodistention alone [46,54]
BoNT-A molecules across the barrier boundary of the bladder mucosa without the need for needle injections, such as using protamine sulfate to disrupt the barrier of the urothelium; electromotive drug delivery and Low-energy shock wave (LESW) to increase the permeability of the urothelium; and liposomes, thermosensitive hydrogel, and hyaluronan–phosphatidylethanolamine to create a carrier for BoNT-A transportation [85]
This study showed that LESW monotherapy in IC/BPS bladders is safe and has a therapeutic effect, especially in pain reduction

Summary

Introduction

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder condition characterized by bladder pain, frequency, and nocturia [1]. Glomerulations after cystoscopic hydrodistention, and denudation of the bladder urothelium are the most common clinical characteristics of IC/BPS, suggesting that bladder inflammation and urothelial dysfunction are the key contributing factors [1,2]. The actual pathophysiology of IC/BPS remains unclear. The apoptotic process in the microvascular endothelial cells and high levels of urothelial cell apoptosis have been detected in IC/BPS bladders [3,4]. Biomedicines 2022, 10, 396 efforts have been made to treat IC/BPS by improving urothelial cell regeneration and ameliorating chronic inflammation. This article reviews recent research into the pathophysiology of IC/BPS and the potential therapeutic effects of low-energy shock wave (LESW)

Chronic Inflammation and Urothelial Dysfunction Are the Fundamental

Deficits of Urothelial Barrier Result in Bladder Pain Syndrome

Intravesical BoNT-A Injection

Liposome-Encapsulated BoNT-A (Lipotoxin)

Platelet-Rich Plasma

LESW Ameliorates Bladder Inflammation and Might Promote Urothelial Cell

Findings

11. Conclusions