The etiology and pathogenesis of interstitial cystitis (IC) and its related condition in men, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has remained elusive. This has hampered development of mechanistic treatment strategies for these common, chronic and distressing medical conditions. We believe that IC and perhaps CP/CPPS are a spectrum of complex but inter-related genetic and acquired diseases resulting from the interaction of several genes regulating immune/inflammatory and neurogenic parameters and environmental factors/circumstances or exposure, culminating in the combination of pain, frequency, urgency and sexual specific symptoms. New research has delineated the dynamic and powerful association of the immune and neurogenic system in pain activation. An immune-modulated neurogenic model of IC illuminating the action of immune derived substances and pain related substances might be important in discovering the determinants of pain, voiding dysfunction and gender specific sexual problems. This inter-related dynamic model of IC disease pathogenesis could be explored for potential avenues leading to novel diagnostic and treatment strategies. We plan to identify and evaluate the sensitivity and specificity of several novel nerve and inflammation related markers in the diagnosis and follow up of IC (and CP/CPPS). By correlating the levels of urine immune and pain related substances to disease mechanisms, severity and progression, we may be able to create a human disease specific model for diagnosis and treatment.