Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.
OBJECTIVE
Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation.


METHODS
Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes.


RESULTS
SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT.


CONCLUSIONS
This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.
Department of Clinical Sciences, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina; Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado. Electronic address: mwnolan@ncsu.edu.
Michael W
MW
Nolan
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Angela J
AJ
Marolf
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado.
E J
EJ
Ehrhart
Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado.
Sangeeta
S
Rao
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Susan L
SL
Kraft
Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado.
Stephanie
S
Engel
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Hiroto
H
Yoshikawa
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Anne E
AE
Golden
Department of Radiation Oncology, Washington University, St. Louis, Missouri.
Todd H
TH
Wasserman
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Susan M
SM
LaRue
D000818:Animals; D001158:Arteries / Q000473:pathology / Q000528:radiation effects; D004195:Disease Models, Animal; D004285:Dogs; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000209:etiology*; D018783:Impotence, Vasculogenic / Q000188:drug therapy / Q000209:etiology; D008297:Male; D010413:Penis / Q000098:blood supply / Q000294:innervation / Q000528:radiation effects*; D011467:Prostate / Q000098:blood supply / Q000294:innervation / Q000528:radiation effects*; D060525:Pudendal Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D011829:Radiation Dosage; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods; D013599:Systole / Q000502:physiology / Q000528:radiation effects; D014680:Veins / Q000473:pathology / Q000528:radiation effects