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

• Published in: Neurourology and urodynamics Vol. 38; no. 1; pp. 97 - 106
• Main Authors: Minami, Akinori, Tanaka, Tomoaki, Otoshi, Taiyo, Kuratsukuri, Katsuyuki, Nakatani, Tatsuya
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2019
• Subjects: Administration, Intravesical; Animals; Biomarkers; Bladder; bladder pain; Body weight; Cystitis; Cystitis - chemically induced; Cystitis - complications; Cystitis - therapy; Edema; endothelial nitric oxide synthase; Female; Fibrosis; Gene expression; Hydrogen peroxide; Hydrogen Peroxide - administration & dosage; Hyperalgesia; Hyperalgesia - etiology; Hyperalgesia - therapy; Hyperbaric oxygen; Hyperbaric Oxygenation; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; interstitial cystitis; Mice; Mice, Inbred ICR; Nitric oxide; Nitric-oxide synthase; Oxidants; Pain perception; Pain Threshold; Rodents; transient receptor potential; Transient receptor potential proteins; Urination; Urination Disorders - etiology; Urination Disorders - therapy; Urodynamics - drug effects; endothelial nitric oxide synthase; hyperbaric oxygen; bladder pain; interstitial cystitis; hydrogen peroxide; transient receptor potential
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.23822

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 (H2O2). 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) H2O2 instillation twice, followed by HBO (100% O2, 2 ATA, 30 min per session) (N = 4); (3) H2O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2O2 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 H2O2‐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 H2O2 instillation. Conclusion These results suggest that HBO contributes to elimination of H2O2‐induced long‐lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.