Exercise decreases stress induced bladder hyperalgesia, voiding frequency and oxidative load

Chronic stress contributes to voiding dysfunction and bladder pain, especially in interstitial cystitis/bladder pain syndrome (IC/BPS). Oxidative stress has been suggested as a main pathophysiological mechanism underlying IC/BPS. Exercise, with its benefits in pain conditions and efficacy in reducing oxidative load, is a promising treatment. This study investigated the efficacy of exercise treatment on stress-induced hyperalgesia and urinary dysfunction in a water-avoidance stress (WAS) model that mimics the main behavioral and histopathological features of IC/BPS. Rats were exposed to WAS for 10 days, followed by three weeks of voluntary running exercise. Pain phenotypes were assessed via von Frey testing, and voiding parameters were evaluated in metabolic cages. Bladder mast cell infiltration was investigated histologically, and permeability was assessed electrophysiologically in Ussing chambers. Biomarkers of oxidative damage, including lipid peroxidation, protein carbonylation, and DNA oxidation, were measured. WAS increased urinary frequency, allodynia, hyperalgesia, and oxidative stress markers. It also increased mast cell infiltration in the bladder and impaired bladder permeability. Exercise treatment significantly reduced WAS-induced increases in voiding frequency, allodynia, and hyperalgesia. Exercise also increased total antioxidant capacity and reduced oxidative damage markers to control levels. WAS replicates key features of IC/BPS, and exercise ameliorates its effects through antioxidant mechanisms.