Jiang Yuan-Hong, Jhang Jia-Fong, Lee Yu-Khun, Kuo Hann-Chorng
Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Buddhist Tzu Chi University, Hualien 97004, Taiwan.
Biomedicines. 2022 Feb 7;10(2):396. doi: 10.3390/biomedicines10020396.
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.
低能量冲击波（LESW）疗法已知可促进组织再生，具有镇痛和抗炎作用。LESW治疗已被证明对治疗慢性前列腺炎、盆腔疼痛综合征以及膀胱过度活动症有效，并且对人类间质性膀胱炎/膀胱疼痛综合征（IC/BPS）有潜在作用。LESW可减轻疼痛行为，下调神经生长因子表达，并通过降低炎症蛋白的表达来抑制膀胱过度活动。先前的大鼠IC模型表明，LESW可增加尿路上皮通透性，促进膀胱内注射肉毒杆菌毒素A（BoNT-A），并阻断乙酸诱导的膀胱过度活动，这表明LESW可能是缓解膀胱炎症性疾病（如膀胱超敏反应、IC/BPS和膀胱过度活动症）的潜在治疗方法。最近的一项临床试验表明，LESW单一疗法可使疼痛评分和IC症状显著降低。BoNT-A逼尿肌注射或脂质体包裹的BoNT-A灌注也可抑制炎症并改善IC症状。然而，BoNT-A注射需要麻醉，且可能会出现某些并发症。我们每周使用LESW加膀胱内BoNT-A灌注的初步研究表明，总体反应评估有所改善，且无任何不良事件。此外，一项免疫组织化学研究显示，IC膀胱组织的尿路上皮下存在裂解的SNAP25蛋白，这表明在应用LESW后，BoNT-A可穿透尿路上皮屏障。这些结果为LESW加BoNT-A灌注这种新型IC/BPS治疗方法的有效性和安全性提供了证据，该方法无需麻醉，也无需膀胱注射。本文综述了目前关于LESW以及LESW加膀胱内治疗药物对膀胱疾病的证据，以及这种新型IC/BPS微创治疗模型的病理生理学和药理学机制。
