Nezu Kunihisa, Yamashita Shinichi, Koyama Juntaro, Goto Takuro, Suzuki Yu, Sato Takuma, Kawasaki Yoshihide, Kawamorita Naoki, Ito Akihiro
Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Sex Med. 2025 Jun 3;22(6):1006-1013. doi: 10.1093/jsxmed/qdaf092.
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.
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.
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.
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.
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).
IMI improves SV function, suggested that IMI might be useful in patients with EjD.
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.
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.
腹主动脉周围手术，包括睾丸癌腹膜后淋巴结清扫术，常导致外周交感神经损伤，进而引发射精功能障碍（EjD）。EjD会降低性活动和男性生育能力。丙咪嗪（IMI）已被经验性地用于治疗EjD。然而，关于EjD的动物模型研究和临床研究有限。
我们使用阿扑吗啡（APO）诱导射精和腰内脏神经（LSN）电刺激，研究IMI对去神经损伤大鼠EjD模型的影响。
36只雄性Sprague-Dawley大鼠分为6组：假手术组、假手术-IMI组、挤压-赋形剂组、挤压-IMI组、切断-赋形剂组和切断-IMI组。挤压组双侧HGN被挤压，切断组双侧HGN被切除。HGN损伤后7-30天腹腔注射IMI（1mg/kg）或赋形剂。
挤压-IMI组在HGN损伤后21天和28天，平均精液固体重量显著高于挤压-赋形剂组（分别为P = 0.011和P = 0.036）。然而，切断-IMI组未观察到精液固体重量增加。挤压-IMI组的ΔSVPA高于挤压-赋形剂组，但差异无统计学意义。此外，挤压-IMI组的ΔSVPE显著高于挤压-赋形剂组（P = 0.024）。另外，HGN损伤后30天，挤压-IMI组的精囊平均重量低于挤压-赋形剂组（P = 0.014）。
IMI改善精囊功能，提示IMI可能对EjD患者有用。
本研究表明IMI通过改善大鼠模型的精囊功能对EjD有影响。局限性包括缺乏IMI作用机制或不同剂量对EjD影响的研究。
该模型可全面评估大鼠的EjD，IMI可减轻HGN损伤后的EjD。有助于阐明神经损伤相关EjD的机制并开发治疗方法。
