(214) A REVIEW OF BASIC SCIENCE STUDIES SUPPORTING LOW INTENSITY SHOCKWAVE THERAPY AS A DISEASE MODIFYING TREATMENT FOR VASCULOGENIC ERECTILE DYSFUNCTION
Authors: Kim N , Kim NN , Goldstein SW 
Published: December 2024

Abstract

Introduction
Low intensity shockwave therapy (LiSWT) for ED attempts to address the underlying vascular pathophysiology of poor cavernosal tissue expandability and reduced cavernosal arterial inflow, unlike ED symptomatic treatments (PDE5 inhibitors, vasoactive agent self-injections) that aim to maximize smooth muscle relaxation. LiSWT induces mechanotransduction expansion/contraction effects on erectile tissue cells. The mechanotransduction mechanical stimuli are then converted into biochemical signal activation in these erectile tissue cells. The activations of biochemical signals in erectile tissue cells acts to increase the density of endogenous mesenchymal stem cells, increase downstream cavernosal smooth muscle synthesis and increase the release of vasodilating factors such as nitric oxide.

Objective
To review contemporary basic science studies delineating the biochemical changes induced by LiSWT through mechanotransduction for disease modification of vascular pathology causing ED.

Methods
Pubmed and Google Scholar were searched between January 2024 and May 2024 for articles containing the following keywords individually and in combination: LiSWT and animal models of ED, mechanotransduction, mesenchymal progenitor/penile stem cells, cavernosal smooth muscle synthesis, vasodilating factors, angioneogenesis, and nitric oxide.

Results
A total of 22 articles were reviewed, with a focus on animal models of ED. LiSWT to the penis induces mechanotransduction and resultant biochemical changes in the erectile tissue cells of animal models of ED. LiSWT to the penis was found to improve erectile function in streptozotocin-induced and Goto-Kakizaki diabetic rats, obesity rats, spontaneously hypertensive rats, bilateral cavernous nerve injury and internal pudendal bundle ligation rats, and naturally aged Wistar rats. LiSWT significantly increased endogenous mesenchymal stem cell density, cavernosal neuronal nitric oxide synthase expression, and cavernosal smooth muscle content in treated versus untreated diabetic rats (Qiu et al). LiSWT in diabetic rats showed increased cavernosal α-smooth muscle actin concentration; and nitric oxide and guanosine 3',5'-cyclic monophosphate levels mediating vasodilation significantly increased in cavernosal smooth muscle (Shin et al). LiSWT differentiated penile progenitor cells into smooth muscle through activation of the Wnt/b-catenin signaling pathway (Peng et al). LiSWT increased cavernosal smooth muscle content and improved cavernosal smooth muscle/collagen ratio in 12-week-old Zucker fatty rats compared to controls (Ruan et al) and in spontaneous hypertensive rats (Assaly et al). LiSWT had an anti-fibrotic effect in streptozotocin-induced diabetic rats (Lei et al).

Conclusions
A review of basic science studies reveal that the mechanism of action of LiSWT for ED appears related, in part, to mechanotransduction. In the penis, mechanotransduction is the shockwave energy-induced contraction and expansion of cavernosal erectile tissue inducing biologic changes including increases in endogenous mesenchymal stem cell density. It is hypothesized that these progenitor stem cells differentiate into various downstream cells, including cavernosal smooth muscle and endothelial cells, resulting in improved veno-occlusive function and vasodilation respectively in the corpora cavernosa. LiSWT for ED is a disease modifying strategy that addresses the underlying vascular pathophysiology of ED. Future studies should address use of LiSWT for ED in combination with symptomatic ED treatments, such as PDE5 inhibitors and penile self-injection therapy, as both strategies maximize conservative, non-operative ED management.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Softwave/TRT.