European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction

Abstract

Introduction Rodent animal models are currently the most used in vivo model in translational studies looking into the pathophysiology of erectile dysfunction after nerve-sparing radical prostatectomy. Aim This European Society for Sexual Medicine (ESSM) statement aims to guide scientists toward utilization of the rodent model in an appropriate, timely, and proficient fashion. Methods MEDLINE and EMBASE databases were searched for basic science studies, using a rodent animal model, looking into the consequence of pelvic nerve injury on erectile function. Main outcome measures The authors present a consensus on how to best perform experiments with this rodent model, the details of the technique, and highlight possible pitfalls. Results Owing to the specific issue—basic science—Oxford 2011 Levels of Evidence criteria cannot be applied. However, ESSM statements on this topic will be provided in which we summarize the ESSM position on various aspects of the model such as the use of the Animal Research Reporting In Vivo Experiments guideline and the of common range parameter for nerve stimulation. We also highlighted the translational limits of the model. Conclusion The following statements were formulated as a suggestive guidance for scientists using the cavernous nerve injury model. With this, we hope to standardize and further improve the quality of research in this field. It must be noted that this model has its limitations. Weyne E, Ilg MM, Cakir OO, et al. European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction. Sex Med 2020;8:327–337.

Acetyl‐L‐carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration

“…nerve damage and erectile tissue injury, which was also recommended by the consensus statement. 32 By the above methods, we identified that erectile function was significantly impaired in the BCNI group, which is similar to previous reports. 33 Furthermore, cavernosal denervation can dampen erectile function through mechanisms like increased collagen content, fibrosis, apoptosis, penile endothelial dysfunction, and oxidative stress injury.…”

“…Also, to ensure the homogeneity of the study, we used the same microsurgical clamp for all rats' cavernous nerves to maintain consistent clamping force. Moreover, we stimulated the CN between the MPG and the nerve injury site during evaluating the erectile dysfunction to analyze both nerve damage and erectile tissue injury, which was also recommended by the consensus statement 32 . By the above methods, we identified that erectile function was significantly impaired in the BCNI group, which is similar to previous reports 33 .…”

“…According to the European Society for Sexual Medicine consensus statement on the use of the cavernous nerve injury rodent model, we created a BCNI rat model by clamping bilateral CN distally at distal MPG for 2 min, which is considered to be the gold standard and most reliable to study erectile function recovery. 32 Also, to ensure the homogeneity of the study, we used the same microsurgical clamp for all rats' cavernous nerves to maintain consistent clamping force. nerve damage and erectile tissue injury, which was also recommended by the consensus statement.…”

Rectification of cavernosal fibrosis and veno‐occlusive dysfunction by administration of suberoylanilide hydroxamic acid in a rat model of cavernosal nerve injury: Comparison with a PDE5 inhibitor

“…Also, the safety issue including adverse effects by selective HDAC inhibitors needs to be addressed by well‐designed clinical studies in future, because animal models might not reflect the human situation. Second, the clinical benefit of penile rehabilitation using a variety of therapeutic strategies for preventing permanent post‐RP ED has not been confirmed in most of the well‐designed clinical trials, despite the promising results by the therapeutic strategies in animal models of CN injury 8‐12,21 . This indicates that animal models might not reflect the human situation.…”

“…Fifty‐six 12‐week‐old rats, weighing 330‐360 g, were randomized into the four groups (fourteen rats per each group): sham surgery treated with saline vehicle [Group S], bilateral CNCI treated with saline vehicle [Group I], CNCI treated with SAHA (vorinostat; Selleckchem, Houston, USA), a pan‐HDAC inhibitor [Group V], and CNCI treated with an udenafil (Dong‐A, Seoul, Korea), a PDE5 inhibitor [Group P]. The sham surgery and CNCI were performed by an experienced surgeon who was blinded to group allocation, according to a recent European Society for Sexual Medicine Consensus Statement 14,21 . Briefly, after the rats were anesthetized using 10 mg/kg zoletil (Vibac Laboratories, Carros, France), the lower abdominal midline incision was performed, and the bilateral major pelvic ganglia (MPGs) were identified.…”