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Lacosamide alleviates bilateral cavernous nerve injury-induced erectile dysfunction in the rat model by ameliorating pathological changes in the corpus cavernosum

International Journal of Impotence Research (2023)Cite this article

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Abstract

Bilateral cavernous nerve injury-related erectile dysfunction (BCNI-ED) shows a limited response to type 5 phosphodiesterase inhibitors. Furthermore, lacosamide (LCM) can alleviate peripheral neuropathy. To explore whether LCM can improve the erectile response after BCNI, we randomly divided 30 young Sprague-Dawley rats into three groups (n = 10 per group), namely, the sham operation, 0.9% normal saline-treated (BCNI + 0.9% NS), and LCM-treated BCNI (BCNI + LCM) groups. LCM was injected intraperitoneally at a dose of 90 mg/kg/day for 7 consecutive days. Erectile function was assessed by measuring the ratio of peak intracavernous pressure (ICP) to mean arterial pressure (MAP), and tissues were harvested for transmission electron microscopy, immunofluorescence, Masson’s trichrome staining, TUNEL staining, and Western blot analysis. The BCNI + 0.9% NS group showed reduced ICP/MAP ratio (0.93 ± 0.04 vs. 0.44 ± 0.05, P < 0.0001). An increased proportion of TUNEL-positive cells (0.04 ± 0.01 vs 0.87 ± 0.03, P < 0.0001) and a decreased smooth muscle/collagen ratio (0.44 ± 0.01 vs. 0.33 ± 0.01, P < 0.001) were observed in the BCNI + 0.9% NS compared with the sham group. Administration of LCM significantly restored the ICP/MAP ratio (0.44 ± 0.05 vs. 0.74 ± 0.05, P < 0.001) and decreased the proportion of TUNEL positive cells (0.87 ± 0.03 vs. 0.60 ± 0.04, P < 0.0001) in the corpus cavernosum following BCNI. The ratio of smooth muscle to collagen (0.43 ± 0.01vs. 0.33 ± 0.01, P < 0.01) and expression of α-SMA (P < 0.0001) in the BCNI + LCM group significantly increased compared with BCNI + 0.9% NS group, indicating alleviation of fibrosis. Apoptotic markers, including Bax/Bcl-2 (P < 0.01) and Caspase-3 (P < 0.0001) in the BCNI + LCM group was significantly lower than that in the BCNI + 0.9% NS group. LCM treatment partially upregulated the expression of vWF and eNOS in cavernous tissue in rats subjected to BCNI (P < 0.05). Increases in S100-β and nNOS expression in the major pelvic ganglion (MPG) were observed after LCM administration. In summary, LCM can recover erectile function in BCNI-ED rat model by suppressing corporal apoptosis and fibrosis, and protecting the cavernous nerve.

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Fig. 1: Analysis of the anatomical structure of the MPG and CN and in the three groups via TEM.
Fig. 2: Effect of LCM on erectile function of rats in each group.
Fig. 3: LCM treatment reduces cell apoptosis in the corpus cavernosum subjected to BCNI.
Fig. 4: Administration of LCM increases smooth muscle content and reduces corpus cavernosum fibrosis in rats subjected to BCNI.
Fig. 5: LCM treatment can increase the expression of endothelium-related markers in cavernous tissue of rats subjected to BCNI.
Fig. 6: LCM treatment can promote the regeneration of MPG.

Data availability

The authors declare the availability of data upon request.

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Acknowledgements

We would like to thank the researchers and The Urology and Andrology Laboratory of The First Affiliated Hospital of Nanjing Medical University for the contributions.

Funding

This article was funded by the National Natural Science Foundation of China [grant number: 82071638; 81801438].

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Author notes

  1. These authors contributed equally: Liangyu Yao, Rong Cong, Xuan Zhou.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Liangyu Yao, Rong Cong, Xuan Zhou, Xiang Zhou, Chengjian Ji, Xiyi Wei, Xianghu Meng & Ninghong Song

  2. Department of Urology, The Affiliated Kezhou People’s Hospital of Nanjing Medical University, Kezhou, Xinjiang, 845350, China

    Ninghong Song

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Contributions

NS designed the project; LY, RC, and Xuan Zhou drafted the manuscript; LY, RC, Xuan Zhou, and Xiang Zhou carried out the experiments. NS and XM guided the experiment directions and edited the manuscript. XW and CJ conducted the statistical analysis. All authors read and approved the final manuscript version.

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Correspondence to Xianghu Meng or Ninghong Song.

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Yao, L., Cong, R., Zhou, X. et al. Lacosamide alleviates bilateral cavernous nerve injury-induced erectile dysfunction in the rat model by ameliorating pathological changes in the corpus cavernosum. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00674-9

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