Hyperbaric oxygen significantly improves frequent urination, hyperalgesia, and tissue damage in a mouse long-lasting cystitis model induced by an intravesical instillation of hydrogen peroxide

Neurourol Urodyn. 2019 Jan;38(1):97-106. doi: 10.1002/nau.23822. Epub 2018 Nov 9.

Abstract

Aim: To investigate whether hyperbaric oxygen (HBO) is effective for the pathophysiological findings in an IC/PBS-like mouse model induced by intravesical hydrogen peroxide (H2 O2 ).

Methods: Six-week-old ICR female mice (N = 16) were divided into four experimental groups: (1) sham control with intravesical vehicle instillation twice, and without subsequent treatment (N = 4); (2) H2 O2 instillation twice, followed by HBO (100% O2 , 2 ATA, 30 min per session) (N = 4); (3) H2 O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2 O2 instillation twice, followed by no treatment (N = 4). Body weight, voiding frequency, tidal voiding volume, and individual bladder pain threshold using the von-Frey test were measured. Whole body uptake of an inflammation-specific fluorescent pan-cathepsin was assessed by an in vivo imaging. Immunohistochemical staining and the mRNA expression of several biomarkers associated with chronic inflammation in resected bladders were evaluated.

Results: The HBO-treated group showed significant improvement in voiding frequency, tidal voiding volume, and the individual bladder pain threshold. Moreover, HBO markedly suppressed H2 O2 -induced inflammation, edema, and fibrosis in bladder wall, concomitant with a significant decrease in mRNA expressions of inflammation biomarkers and a significant increase in endothelial nitric oxide synthase expression. HBO also inhibited the expression of transient receptor potential channels induced by H2 O2 instillation.

Conclusion: These results suggest that HBO contributes to elimination of H2 O2 -induced long-lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.

Keywords: bladder pain; endothelial nitric oxide synthase; hydrogen peroxide; hyperbaric oxygen; interstitial cystitis; transient receptor potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Animals
  • Cystitis / chemically induced
  • Cystitis / complications*
  • Cystitis / therapy*
  • Female
  • Hydrogen Peroxide* / administration & dosage
  • Hyperalgesia / etiology*
  • Hyperalgesia / therapy*
  • Hyperbaric Oxygenation*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred ICR
  • Oxidants*
  • Pain Threshold
  • Urination Disorders / etiology*
  • Urination Disorders / therapy*
  • Urodynamics / drug effects

Substances

  • Oxidants
  • Hydrogen Peroxide