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An evolving hypothesis on the mechanism and efficacy of intracavernosal injection of botulinum toxin to improve erectile function: an animal study in aging rats

Punjani, N1; Campbell, J2; De Young, L1; Henriquez, K3; Radomski, S4; Alzubaidi, R5; Gros, R1; Brock, G1

1: Western University, London, ON, Canada; 2: John Hopkins, Baltimore, MA, USA; 3: Western University, Canada; 4: University of Toronto, Toronto, ON, Canada; 5: Hamad Medical Corporation, Doha, Qatar

Introduction & Objectives: Erectile dysfunction (ED) is a common problem for aging males which significantly impacts both patient and partner quality of life. Current treatment options do not offer long-standing efficacy and therefore a more durable and sustainable treatment is needed. Our previous work has demonstrated that botulinum toxin (BTX) improves erectile function in an aging rat model. We aim to determine the duration of BTX effects and elucidate the mechanism of action as it pertains to penile smooth muscle function.

Materials & Methods: Twenty male Sprague Dawley rats with an average age of 15 months were divided into four experimental groups: Control (NS), BTX 3 days (BTX3D), BTX 1 week (BTX1W) and BTX 2 weeks (BTX2W). The rats received an intracavernous injection of either 10 units of BTX in 80ul normal saline (NS) or 80ul of NS as a control. Rats were observed for either 3 days, 1 week, or 2 weeks after injection. Erectile function was assessed by cavernous nerve electro-stimulation induced intracavernous pressure (ICP). Functional assessments of penile vascular reactivity were carried out by analysing ICP changes in response to either methacholine (MCH) or sodium nitroprusside (SNP) in both BTX and control groups.

Results: There were no complications after intracavernous injections of BTX or NS, however, weight loss was observed in the BTX2W rats. The BTX groups all demonstrated a significantly higher ICP when compared to control animals. There was an increase in ICP induced by SNP observed after 3 days, which returned to baseline 2 weeks after BTX injection, and a trend of increased ICP using MCH after 2 weeks compared to the other groups, however these were not statistically significant.

Conclusions: Our study confirms that intracavernous injection of BTX improves erectile function in aging rats. We observed a durable response to BTX with a maximal benefit 3 days after injection and a residual effect persisting up to 2 weeks. While the mechanism of action has not been fully elucidated, we illustrate that adjunctive therapies working through alterative pathways may be used to potentiate and enhance the effect of BTX.  


Work supported by industry: no. The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.

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