Oxidative Stress and Chronic Inflammation as Partners in Crime in Interstitial Cystitis/Bladder Pain Syndrome

BACKGROUND: 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. SUMMARY: 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. KEY MESSAGES: 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.