Effects of Low-Energy Shockwave Therapy on the Erectile Function and Tissue of a Diabetic Rat Model

Abstract

Introduction Low-energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). However, the underlying mechanism remains unknown. Aim To investigate whether LESWT can ameliorate DM-associated ED in a rat model, and examine the associated changes in the erectile tissues. Methods Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU, 50mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, 8 of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group) while another 8 rats were subject to shockwave treatment (DM+SW group). Each rat in the DM+SE group received 300 shocks at energy level of 0.1mJ/mm2 and frequency of 120/min. This procedure was repeated three times a week for two weeks. Another two weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. Main Outcome Measures Erectile function was measurement by ICP. Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence (IF) staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively. Results STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents. These DM-associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU+ cells) were significantly more numerous in DM+SW than in DM rats. Conclusions LESWT can partially ameliorate DM-associated ED by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis. These beneficial effects appear to be mediated by recruitment of endogenous MSCs.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model

“…It was thus shown that Li-ESWT triggers the activation of various intracellular signaling pathways causing upregulation of numerous angiogenic factors (i.e., VEGF…) to promote neovascularization and mobilizes the recruitment of endogenous progenitor cells thereby favoring angiogenesis and tissue regeneration in cardiovascular medicine and wound healing (17)(18)(19)(20)(21). These pro-angiogenic signaling pathways and recruitment of endogenous progenitor cells have also been shown to be activated in the penile tissue following Li-ESWT treatment in diabetic ED models (15,16), despite the fact that it does not upregulate the NO/cGMP pathway (14). Moreover, the role of Li-ESWT in the regeneration of peripheral nerves has also been previously suggested after nerve compression or in a model of autologous nerve graft (22,23) and later investigated in the context of erectile function recovery in diabetic ED models (15,16).…”

“…These pro-angiogenic signaling pathways and recruitment of endogenous progenitor cells have also been shown to be activated in the penile tissue following Li-ESWT treatment in diabetic ED models (15,16), despite the fact that it does not upregulate the NO/cGMP pathway (14). Moreover, the role of Li-ESWT in the regeneration of peripheral nerves has also been previously suggested after nerve compression or in a model of autologous nerve graft (22,23) and later investigated in the context of erectile function recovery in diabetic ED models (15,16).…”

“…To date, however, very few preclinical studies have been led to investigate these aspects (14)(15)(16).…”

Un nuevo enfoque terapéutico para la disfunción eréctil: las ondas de choque de baja intensidad

“…Estos medicamentos son efectivos antes del acto sexual, pero no logran mejorar las erecciones espontáneas y su efecto es esencialmente limitado en el tiempo (7,24). Hasta 30% de los pacientes presentan efectos adversos de moderados a graves o tienen contraindicaciones para la toma de estos medicamentos, entre ellas, los intolerantes a los efectos secundarios (cefalea principalmente) y los que toman nitratos para la angina de pecho (25,26).…”

“…Los resultados invariablemente apuntan a la inducción de la angiogénesis como uno de los mecanismos subyacentes a los efectos de la terapia con estas ondas. Además, uno de estos estudios también identificó como un posible mecanismo el reclutamiento de células madre mesenquimales (25,43). Nishida y colaboradores (44) propusieron un modelo porcino de disfunción miocárdica inducida por isquemia y encontraron que la terapia con ondas de choque de baja intensidad regula la expresión del VEGF en el miocardio isquémico y mejora el flujo sanguíneo miocárdico regional y la fracción de eyección ventricular izquierda, lo que podría explicar los resultados obtenidos en la DE.…”