Potential Mechanisms Underlying the Increased Excitability of the Bladder Afferent Pathways in Interstitial Cystitis/Bladder Pain Syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating disorder associated with lower urinary tract symptoms, including frequency, urgency, and suprapubic pain, which inconveniences the patients and seriously impairs their quality of life. Although the etiology of IC/BPS is unknown, intense research has been conducted focusing on the involvement of the bladder afferent nerve in regard to the cellular mechanisms underlying neurogenic inflammation of the urinary bladder. The involvement of neurogenic inflammation in patients with IC/BPS is supported by several animal models of bladder inflammation as well as clinical studies. Chronic bladder inflammation can result in functional and anatomical changes in the primary afferent neurons through the expression of inflammationrelated proteins/receptors in the urinary bladder and bladder afferent pathways, leading to pain symptoms in patients with IC/BPS. In addition, neurogenic inflammation of the bladder mucosa can induce the central sensitization as well as the peripheral sensitization, and the neuroimmune overactivity and toll-like receptor (TLR) signaling of the immune cells involve complex mechanisms of central sensitization. This review presents the potential mechanisms underlying the afferent hyperexcitability of the bladder in IC/BPS and summarizes the neurogenic inflammation, neurotrophic factors, TLRs, and neuroimmune communication.