Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. Multiple treatment options exist, including behavioural interventions, oral medications, intravesical instillations and procedures such as hydrodistension; however, many clinical trials fail, and patients experience an unsatisfactory treatment response, likely owing to IC/BPS phenotype heterogeneity and the use of non-targeted interventions. Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. The development of new models in which these pathways can be manipulated will aid this research and enable further investigation of promising therapeutic targets.

Nature reviews. Urology. 2024 Feb 07 [Epub ahead of print]

Ashu Mohammad, Mallory A Laboulaye, Chen Shenhar, Amy D Dobberfuhl

Department of Urology, Stanford University School of Medicine, Palo Alto, CA, USA., Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA., Department of Urology, Stanford University School of Medicine, Palo Alto, CA, USA. .