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


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 microg (low concentration), or 20 microg 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) cmH(2)O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH(2)O. 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) cmH(2)O, vs 24.3 (5.9) cmH(2)O for 20 microg 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.


CONCLUSIONS
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-microg dose giving the most promising results.
Fandel
Thomas M
TM
Johannes Gutenberg-University School of Medicine, Mainz, Germany.
Bella
Anthony J
AJ
Tantiwongse
Kavirach
K
Garcia
Maurice
M
Nunes
Lora
L
Thüroff
Joachim W
JW
Tanagho
Emil A
EA
Pohl
Jens
J
Lue
Tom F
TF
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy; D055428:Growth Differentiation Factor 5; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D010413:Penis / Q000294:innervation*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020196:Trauma, Nervous System / Q000188:drug therapy*
D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5