Molecular mechanisms of penile traction for penile rehabilitation in a bilateral cavernous nerve crush injury rat model

Brian Dick; Jacob W Greenberg; Michael Polchert; Max Moore; Joseph Kim; Cameron Belding; Hogyoung Kim; Suresh C Sikka; Asim Abdel-Mageed; Shams Halat; Wayne J G Hellstrom

doi:10.21037/tau-23-53

Molecular mechanisms of penile traction for penile rehabilitation in a bilateral cavernous nerve crush injury rat model

Transl Androl Urol. 2023 Aug 31;12(8):1219-1228. doi: 10.21037/tau-23-53. Epub 2023 Aug 4.

Authors

Affiliations

¹ Department of Urology, University of California San Francisco, San Francisco, CA, USA.
² Department of Urology, School of Medicine, Tulane University, New Orleans, LA, USA.
³ School of Science and Engineering, Tulane University, New Orleans, LA, USA.
⁴ Division of Basic Pharmaceutical Sciences, Xavier University, New Orleans, LA, USA.
⁵ Department of Pathology, Tulane University, School of Medicine, New Orleans, LA, USA.

^# Contributed equally.

Abstract

Background: Prostate cancer is the most common solid-organ malignancy in adult men. Early detection and treatment of prostate cancer with radical prostatectomy (RP) has improved cancer-specific survival but is associated with penile shortening and erectile dysfunction. Penile traction therapy (PTT) has been demonstrated to increase stretched penile length (SPL) prior to penile prosthesis placement and may improve erectile function (EF) in patients with Peyronie's disease. We aimed to evaluate the efficacy of PTT in preserving penile length and EF after bilateral cavernous nerve crush injury (BCNI) in a rat model.

Methods: Twenty-four male Sprague-Dawley rats aged 11-13 weeks were randomly assigned to three groups (n=8, each): sham operation with no PTT (Sham), BCNI without PTT (Crush), and BCNI with PTT (Traction). PTT was started on postoperative day 3. A traction force of 1 Newton was applied to the penis for 30 minutes each day for 28 days. After 28 days of traction, the cavernous nerve was stimulated while recording the intracavernosal pressure (ICP) and the mean arterial pressure (MAP) simultaneously. Cavernosal tissue was excised, and western blot analysis for endothelial nitric oxide synthase (eNOS) was performed. Significance was determined by using ANOVA with Tukey-Kruger post-hoc testing.

Results: At 4 weeks after nerve injury, the Traction group had significantly greater SPL compared to the Sham and Crush groups (30 vs. 28 and 27 mm, respectively). The Sham group had significantly greater EF (ΔICP/MAP) compared to the Crush group at 2.5, 5, and 7.5 V. The EF of the Traction group was between that of the Sham and Crush groups and was not significantly different from the Sham group at any voltages. Further downstream analysis revealed that the Traction group had significantly greater eNOS expression in cavernosal tissue compared to the Crush group, which was confirmed on western blot analysis and immunohistochemistry (IHC) staining.

Conclusions: Findings from this animal study suggest that PTT has the potential to mitigate penile retraction after RP. While more studies are needed to determine the effect of PTT on preservation of EF, the increased eNOS expression observed in the Traction group offers a potential protective mechanism of action.

Keywords: Penile rehabilitation; endothelial nitric oxide synthase (eNOS); erectile dysfunction; mechanism of action; penile traction therapy (PTT).