title: Pelvic nerve injury negatively impacts female genital blood flow and induces vaginal fibrosis-implications for human nerve-sparing radical hysterectomy.
abstract: OBJECTIVE
  This study sought to develop a novel animal model to study the impact of nerve-sparing radical hysterectomy (NSRH) on female genital blood flow.
  
  
  METHODS
  In vivo animal study.
  
  
  METHODS
  Thirty Sprague-Dawley female rats.
  
  
  METHODS
  Female rats underwent either unilateral pelvic nerve (PN) crush (PNC; n = 9), or crush of both the PNs and all efferent nerves in the pelvic plexus ('clock-nerve crush', CNC; n = 9). Under anaesthesia, we electrically stimulated the crushed PN at 3 and 10 days after crush while monitoring blood pressure and recording clitoral and vaginal blood flows by laser Doppler. Uninjured PNs were stimulated as an internal control. Twelve additional rats were assigned either to bilateral PNC or sham surgery, and genital tissues were processed 10 days after injury for in vitro analysis.
  
  
  METHODS
  Genital blood flow, nNOS, eNOS, collagen I-III.
  
  
  RESULTS
  Stimulation of the crushed PN in both groups subjected to PNC and CNC induced significantly lower peak genital blood flow at 3 and 10 days (P < 0.05) compared to stimulation of the non-crushed control PN. The immunofluorescence and Western blot analyses revealed that all injured rats exhibited more vaginal collagen III and collagen I than rats did that ad undergone sham surgeries (P < 0.05). PCN reduced nNOS expression in both clitoral and vaginal tissue.
  
  
  CONCLUSIONS
  Based on our study it may be hypothesised that NSRH might cause reductions of genital blood flow and vaginal fibrosis due to neurapraxia of the pelvic nerve and reductions of nNOS nerve fibres in clitoral and distal vaginal tissue.
  
  
  CONCLUSIONS
  Pelvic nerve neurapraxia during nerve-sparing radical hysterectomy could lead to sexual arousal dysfunction.
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Castiglione
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Division of Oncology/Unit of Gynecology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bergamini
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Laboratory for Experimental Urology, Gene and Stem Cells Applications, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Albersen
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hannan
authors.affiliation: The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bettiga
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benigni
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Salonia
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Clinical Pharmacology, Linköping, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002987:Clitoris / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D007001:Hypogastric Plexus / Q000293:injuries*; D007044:Hysterectomy / Q000009:adverse effects* / Q000379:methods*; D017078:Laser-Doppler Flowmetry; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010388:Pelvis / Q000294:innervation; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D014621:Vagina / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D019001:Nitric Oxide Synthase
keywords: Blood flow; clitoris; female sexual dysfunction; laser Doppler; neurapraxia; pelvic nerve injury; radical hysterectomy; vagina