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Effect of imipramine on ejaculatory dysfunction in a rat hypogastric nerve injury model
Kunihisa Nezu1, Shinichi Yamashita1, Juntaro Koyama1
1Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Background:
Peripheral sympathetic nerve injury, resulting from surgery around the abdominal aorta, including retroperitoneal lymph node dissection for testicular cancer, often causes ejaculatory dysfunction (EjD). EjD reduces sexual activity and male fertility. Imipramine (IMI) has been empirically used for EjD. However, research using animal models and clinical studies on EjD is limited.
Aim:
We investigated the effects of IMI in a rat model of EjD following hypogastric nerve (HGN) injury using apomorphine (APO)-induced ejaculations and lumbar splanchnic nerve (LSN) electrostimulation.
Methods:
Thirty-six male Sprague-Dawley rats were divided into six groups: Sham, Sham-IMI, Crush-Vehicle, Crush-IMI, Cut-Vehicle, and Cut-IMI. In the Crush group, the bilateral HGNs were crushed, and in the Cut group, the bilateral HGNs were excised. IMI (1 mg/kg) or Vehicle was administered intraperitoneally 7-30 days after HGN injury.
Outcomes:
Ejaculatory function was assessed weekly using the weight of solid semen ejaculated from the urethral meatus after subcutaneous administration of 0.5 mg/kg APO. Changes in seminal vesicle pressure (SVP) were assessed using APO-induced ejaculation (ΔSVPA) and LSN electrostimulation (ΔSVPE) 30 days after HGN injury. Dunnett's test was used to determine significant differences between groups.
Results:
In the Crush-IMI group, the mean solid semen weights significantly increased 21 and 28 days after HGN injury compared with those in the Crush-Vehicle group (P = .011 and P = .036, respectively). However, in the Cut-IMI group, no increase in solid semen weight was observed. The ΔSVPA in the Crush-IMI group was higher than that in the Crush-Vehicle group; however, the difference was not statistically significant. Furthermore, ΔSVPE in the Crush-IMI group was significantly higher than that in the Crush-Vehicle group (P = .024). Additionally, the mean seminal vesicle weights in the Crush-IMI group were lower than those in the Crush-Vehicle group at 30 days after HGN injury (P = .014).
Clinical Implications:
IMI improves SV function, suggested that IMI might be useful in patients with EjD.
Strengths And Limitations:
This study shows that IMI has an effect on EjD by improving SV function in a rat model. Limitations include a lack of the mechanisms or the effect of IMI at different doses on EjD.
Conclusion:
This model allowed for the comprehensive assessment of EjD in rats, and IMI attenuated EjD after HGN injury. It aids in the clarification of the mechanism and development of treatments for nerve injury-related EjD.
