title: Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia.
abstract: OBJECTIVE
  Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI.
  
  
  METHODS
  Female Sprague-Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson's trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS).
  
  
  RESULTS
  Bilateral pelvic nerve injury caused larger bladders with less SM content and increased collagen type 1α1 and 3α1 gene expression. At early time points, cholinergic-mediated contraction increased, whereas EFS-mediated contraction decreased and returned to baseline by 30 days. Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. TH nerve terminals surrounding the detrusor decreased in all BPNI groups, whereas VAChT and nNOS terminals decreased 14 and 30 days post-BPNI.
  
  
  CONCLUSIONS
  Bilateral pelvic nerve injury increased bladder size, impaired contractility, and decreased SM and autonomic innervation. Therapeutic strategies preventing nerve injury-mediated decline in neuronal input and SM content may prevent the development of a neurogenic bladder and improve quality of life after invasive pelvic surgery.
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Mail Stop 634, Greenville, NC, 27834-4354, USA. hannanj14@ecu.edu.|The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, 600 North Wolfe Street, Marburg 420, Baltimore, MD, 21287, USA. hannanj14@ecu.edu.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Hannan
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Mail Stop 634, Greenville, NC, 27834-4354, USA.
authors.forename: Shelby A
authors.initials: SA
authors.lastname: Powers
authors.affiliation: The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, 600 North Wolfe Street, Marburg 420, Baltimore, MD, 21287, USA.
authors.forename: Vinson M
authors.initials: VM
authors.lastname: Wang
authors.affiliation: Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.|Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Fabio
authors.initials: F
authors.lastname: Castiglione
authors.affiliation: Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.|Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.affiliation: The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins School of Medicine, 600 North Wolfe Street, Marburg 420, Baltimore, MD, 21287, USA.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D007044:Hysterectomy / Q000009:adverse effects; D018721:Muscarinic Agonists; D059348:Peripheral Nerve Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D001743:Urinary Bladder / Q000294:innervation* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000199:Actins; D003094:Collagen; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; C498862:Acta2 protein, rat
keywords: Autonomic innervation; Detrusor; Neurogenic bladder; Neuropraxia; Radical hysterectomy