title: Pharmacologic and Molecular Characterization of Underactive Bladder Induced by Lumbar Canal Stenosis.
abstract: OBJECTIVE
  To investigate the voiding function in a rat model of lumbar canal stenosis (LCS) using pharmacologic and molecular approaches.
  
  
  METHODS
  Sixty-one female Sprague-Dawley rats were broadly split into a sham and an LCS group. A hole was surgically drilled in the L5-L6 epidural space and filled with a rectangular piece of silicone rubber. Metabolic cage study at week 2 and continuous cystometry (CMG) under urethane anesthesia at weeks 2 and 4 were performed. During CMG, prostaglandin E2 or sulprostone, an prostaglandin E receptor 1 and prostaglandin E receptor 3 agonist was administered locally and intravenously, respectively, and the bladder was then harvested for histology and Western blot.
  
  
  RESULTS
  Compared with sham, the LCS group showed dribbling urination and progressive increase in bladder size. CMG under urethane anesthesia in the LCS group was marked by overflow incontinence and acontractile bladder. Administration of intravesical prostaglandin E2 (200 μM) or intravenous sulprostone (0.1 mg/kg) in the sham group induced bladder overactivity, but decreased the compliance and failed to restore the bladder emptying function in the LCS group. The LCS group showed edematous changes and muscle thinning at week 2, which were partially restored by week 4. Histologic changes were accompanied by downregulation of agrin protein (64.0%) at week 2 and upregulation of M2 receptor (65.4%) at week 4. Expression of M3, protein gene product 9.5, and nerve growth factor did not differ between groups.
  
  
  CONCLUSIONS
  LCS-induced underactive bladder is associated with altered expression of agrin and M2 receptor. The underactive bladder model is clinically relevant, and the findings indicate potential molecular targets for new therapies.
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: Chuang82@ms26.hinet.net.
authors.forename: Yao-Chi
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Urology, Beaumont Health System, Oakland University William Beaumont School of Medicine, Royal Oak, MI.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
mesh_terms: D018171:Agrin / Q000502:physiology*; D000818:Animals; D015536:Down-Regulation; D005260:Female; D008159:Lumbar Vertebrae; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D013130:Spinal Stenosis / Q000150:complications*; D001743:Urinary Bladder / Q000187:drug effects*; D001745:Urinary Bladder Diseases / Q000209:etiology*
chemical_list: D018171:Agrin; D043585:Receptor, Muscarinic M2