The effect of FK1706 on erectile function following bilateral cavernous nerve crush injury in a rat model

• Published in: The Journal of urology Vol. 176; no. 2; p. 824
• Main Authors: Hayashi, Narihiko, Minor, Thomas X, Carrion, Rafael, Price, Raymond, Nunes, Lora, Lue, Tom F
• Format: Journal Article
• Language: English
• Published: United States 01.08.2006
• Subjects: Animals; Disease Models, Animal; Male; Penile Erection - drug effects; Penis - drug effects; Penis - injuries; Penis - innervation; Penis - physiopathology; Rats; Rats, Sprague-Dawley; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology
• ISSN: 0022-5347
• DOI: 10.1016/j.juro.2006.03.071

We investigated the neurotrophic effect of FK1706 on erectile recovery following bilateral cavernous nerve crush injury in a rat model. A total of 28 male Sprague-Dawley rats were randomly divided into 4 equal groups. Seven animals underwent sham operation and subcutaneous vehicle injection, whereas 21 underwent bilateral cavernous nerve crush injury followed by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706 treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function was then assessed by cavernous nerve electrostimulation and penile tissue was evaluated immunohistochemically. No erectile dysfunction was identified in the sham treated group (mean maximal intracavernous pressure +/- SEM 106.8 +/- 6.4 cm H(2)O), whereas nerve injury significantly decreased ICP to 17.9 +/- 7.0 cm H(2)O. FK1706 facilitated neural and erectile recovery in a concentration dependent manner with a mean ICP in the high dose FK treatment group of 80.1 +/- 7.8 cm H(2)O compared with 44.1 +/- 12.9 cm H(2)O in the low dose group. Similar stepwise findings were observed using mean area under the curve data. Sham treated animals showed regular axon sizes and shapes with homogenous GAP-43 and neurofilament staining, whereas injured axons showed irregular shapes, sizes and staining patterns. FK1706 treatment restored axon shape and staining patterns. Injury significantly decreased nicotinamide adenine dinucleotide phosphate staining and FK1706 treatment showed a nonsignificant trend toward increased staining. Bilateral cavernous nerve crush causes reproducible erectile dysfunction, consistent with prior experiments. High dose subcutaneous FK1706 therapy promotes significant neuroregeneration and erectile function recovery.