Long-term functional change of cryoinjury-induced detrusor underactivity and effects of extracorporeal shock wave therapy in a rat model

Int Urol Nephrol. 2019 Apr;51(4):617-626. doi: 10.1007/s11255-019-02095-4. Epub 2019 Feb 22.


Purpose: To investigate the long-term functional change of cryoinjury-induced detrusor underactivity (DU) and the therapeutic potential of repeated low-energy shock wave therapy (LESW).

Methods: Fifty-six female Sprague-Dawley rats were assigned into sham and cryoinjury of bladder with or without LESW (0.05 or 0.12 mJ/mm2; 200 pulses; twice a week for 2 weeks after cryoinjury). Under halothane anesthesia, an incision was made in lower abdomen, and cryoinjury was provoked by bilateral placement of a chilled aluminum rod on the bladder filled with 1 ml saline. Measurement of contractile responses to KCl and carbachol in vitro, conscious voiding, and histological and protein changes were performed on week 1, 2, and 4 after cryoinjury.

Results: Cryoinjury of bladder induced a significant decrease in the detrusor contraction amplitude at week 1 (55.0%) and week 2 (57.2%), but the decrease in the contractile response to KCl and carbachol was only noted at week 1. At week 1, significantly increased COX-2 and TGF-β1 expression accompanied a decrease of VEGF and CGRP expression. At week 4, there was a partial recovery of voiding function and a significant increase in the Ki-67 staining. LESW treatment at higher energy level further amplified the Ki-67 staining and improved the recovery of contraction amplitude and the expression of TGF-β1 and VEGF.

Conclusions: Cryoinjury of detrusor induces DU/UAB with functional impairment lasting for up to 4 weeks, but the associated molecular changes are restored by 2 weeks. LESW improved bladder wall composition, and hastened functional recovery from cryoinjury.

Keywords: Cryoinjury; Detrusor underactivity; Shock wave.

MeSH terms

  • Actins / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Cold Temperature
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Extracorporeal Shockwave Therapy*
  • Female
  • Ki-67 Antigen / metabolism
  • Muscle Contraction / drug effects*
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiopathology*
  • Urinary Bladder, Underactive / etiology
  • Urinary Bladder, Underactive / pathology
  • Urinary Bladder, Underactive / physiopathology*
  • Urinary Bladder, Underactive / therapy*
  • Urination
  • Vascular Endothelial Growth Factor A / metabolism


  • Actins
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Cholinergic Agonists
  • Ki-67 Antigen
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • smooth muscle actin, rat
  • vascular endothelial growth factor A, rat
  • Potassium Chloride
  • Carbachol
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Calcitonin Gene-Related Peptide