The effect of intracavernosal growth differentiation factor-5 therapy in a rat model of cavernosal nerve injury

Authors

  • THOMAS M. FANDEL,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • ANTHONY J. BELLA,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • KAVIRACH TANTIWONGSE,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • MAURICE GARCIA,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • LORA NUNES,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • JOACHIM W. THüROFF,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • EMIL A. TANAGHO,

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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  • JENS POHL,

    1. Biopharm GmbH, Heidelberg, Germany
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  • TOM F. LUE

    1. Departments of Urology, University of California School of Medicine, San Francisco, CA, USA, and Johannes Gutenberg-University School of Medicine, Mainz, and
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Tom F. Lue, Department of Urology, University of California School of Medicine, San Francisco, CA, 94143–0738, USA. e-mail: tlue@urology.ucsf.edu

Abstract

OBJECTIVE

To determine whether the intracavernosal application of growth differentiation factor-5 (GDF-5) influences nerve regeneration and erectile function after cavernosal nerve injury in a rat model.

MATERIALS AND METHODS

Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: eight had a sham operation (uninjured controls), while 24 had bilateral cavernosal nerve crush. The crush-injury groups were treated at the time of injury with an impregnated collagen sponge implanted into the right corpus cavernosum. The sponge contained no GDF-5 (injured controls), 2 µg (low concentration), or 20 µg GDF-5 (high concentration). Erectile function was assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile tissue samples were histochemically evaluated for neuronal nitric oxide synthase (nNOS)-containing fibres in the dorsal penile nerve.

RESULTS

There was no erectile dysfunction in the uninjured control group, as shown by a mean (sem) maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH2O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH2O. After cavernosal nerve injury, the recovery of erectile function was greatest in the low-concentration GDF-5 group; the maximum ICP increase was 40.8 (13.3) cmH2O, vs 24.3 (5.9) cmH2O for 20 µg GDF-5. Histologically, the low-concentration group had significantly more nNOS-containing nerve fibres, at 163 (24.7), than the high-concentration group, at 76 (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls had a mean of 538 (40.6) nerve fibres in the dorsal nerve.

CONCLUSION

Bilateral cavernosal nerve crush resulted in erectile dysfunction with accompanying neurological changes in the rat. The intracavernosal application of GDF-5 enhanced the recovery of erectile function and n-NOS nerve preservation, with a 2-µg dose giving the most promising results.

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