Oxidative stress and chronic inflammation as partners in crime in interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease of the urinary bladder, characterized by chronic pain, increased urinary frequency, urgency, and nocturia. Currently, no therapeutic option consistently provides long-term relief for all IC/BPS patients, likely due to the largely unknown mechanisms underlying the disease's development and progression. IC/BPS is considered a multifactorial disorder with a complex pathobiology that ultimately leads to unresolved inflammation, bladder dysfunction, and pain. Recent research has highlighted chronic inflammation and oxidative stress, resulting from either increased production of reactive oxygen species or their inadequate elimination, as a significant feature of IC/BPS. The frequent co-occurrence of IC/BPS with other chronic diseases characterized by prolonged oxidative stress and subtle chronic inflammation, such as autoimmune diseases, chronic psychological stress, fibromyalgia, and irritable bowel syndrome, suggests a common underlying pathogenic pathway. In this review, we summarize key findings suggesting that oxidative stress and chronic inflammation play a part in the onset and progression of IC/BPS. We explore how oxidative stress contributes to IC/BPS through various mechanisms, including damage to bladder urothelial cells and mitochondria, the activation of innate immune signaling pathways, which together create a self-perpetuating cycle of inflammation. Additionally, we discuss potential therapeutic options and novel drug candidates with anti-inflammatory and antioxidant properties, which could modulate regulatory pathways involved in disease development and provide long-term efficacy in IC/BPS.