Fined by the hallmark symptom of chronic pain described by patients as being localized to the pelvic organs, pelvic floor myofascial support, or external genitalia often accompanied by urinary symptoms, such as urgency or frequency (1-3). IC/BPS occurs in both males and females over a broad age range and across ethnic/racial groups (4). The morbidity of IC/BPS is substantial and often leads to poor quality of life for both patients and their partners (4). IC/PBS diagnosis is primarily based on patient reported symptoms and exclusion of other disorders, due to the lack of consistent CEP-37440 biological activity physical findings. The wide spectrum of symptoms found in IC/BPS suggests that this syndrome may have subgroups which manifest in a similar way clinically but have differing underlying etiologies. The prevalence estimates of IC/BPS vary considerably likely because of differences in source populations and case ascertainment (1). The RAND Interstitial Cystitis Epidemiology (RICE) Study, through a probability sample of U.S. women contacted by telephone, estimated IC/BPS prevalence between 2.7 and 6.53 among person age 18 or older using case definitions of high specificity and high sensitivity, respectively (5). This represent between 3.3 and 7.9 million affected individuals. The RICE Study also estimates IC/BPS prevalence in men between 1.9 and 4.2 (6) while community-based prevalence estimates from the Boston Area Community Health (BACH) Survey suggest 1.3 of U.S. men between the ages of 30 and 79 report symptoms of IC/BPS (7). The bladder has historically been thought to be the origin of IC/BPS symptoms based primarily on patientreported pain, pressure, or discomfort related to filling of this organ. However, this dogma is challenged by observations by the absence of an identifiable bladder pathology in many IC/PBS patients and patients without bladders can continue to report symptoms consistent with this syndrome (8-11). In addition, numerous CEP-37440 web studies have shown IC/BPS is associated with various conditions characterized by chronic pain, such as vulvodynia, endometriosis, fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome [for a review see (12)]; suggesting that central sensitization mechanisms contribute to the manifestation of IC/PBS, at least in some patients. Here we provide an overview of research efforts to characterize IC/BPS and evaluate therapies; when appropriate the possible limitations of this prior work are highlighted.A rationale for developing new strategies to address longstanding and fundamental questions for IC/BPS is also proposed and a number of research and clinical programs that have employed such novel approaches are cited. The importance of collaboration between IC/BPS-focused studies and wider research efforts to promote a more holistic understanding of this syndrome in the context of other urologic and non-urologic disorders is also stressed. These research directions are expected to foster new insights into IC/BPS that may inform future clinical studies and treatment. In this article we restrict our terminology to IC/BPS except in cases where the original reports used other nomenclature. Limitations of past approaches Numerous research studies and clinical trials of IC/BPS have been conducted since the early 1990’s to identify etiology, describe clinical course and risk factors, and identify effective therapies for this syndrome. Efforts to describe fundamental IC/BPS pathophysiology have addressed a broad set o.Fined by the hallmark symptom of chronic pain described by patients as being localized to the pelvic organs, pelvic floor myofascial support, or external genitalia often accompanied by urinary symptoms, such as urgency or frequency (1-3). IC/BPS occurs in both males and females over a broad age range and across ethnic/racial groups (4). The morbidity of IC/BPS is substantial and often leads to poor quality of life for both patients and their partners (4). IC/PBS diagnosis is primarily based on patient reported symptoms and exclusion of other disorders, due to the lack of consistent physical findings. The wide spectrum of symptoms found in IC/BPS suggests that this syndrome may have subgroups which manifest in a similar way clinically but have differing underlying etiologies. The prevalence estimates of IC/BPS vary considerably likely because of differences in source populations and case ascertainment (1). The RAND Interstitial Cystitis Epidemiology (RICE) Study, through a probability sample of U.S. women contacted by telephone, estimated IC/BPS prevalence between 2.7 and 6.53 among person age 18 or older using case definitions of high specificity and high sensitivity, respectively (5). This represent between 3.3 and 7.9 million affected individuals. The RICE Study also estimates IC/BPS prevalence in men between 1.9 and 4.2 (6) while community-based prevalence estimates from the Boston Area Community Health (BACH) Survey suggest 1.3 of U.S. men between the ages of 30 and 79 report symptoms of IC/BPS (7). The bladder has historically been thought to be the origin of IC/BPS symptoms based primarily on patientreported pain, pressure, or discomfort related to filling of this organ. However, this dogma is challenged by observations by the absence of an identifiable bladder pathology in many IC/PBS patients and patients without bladders can continue to report symptoms consistent with this syndrome (8-11). In addition, numerous studies have shown IC/BPS is associated with various conditions characterized by chronic pain, such as vulvodynia, endometriosis, fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome [for a review see (12)]; suggesting that central sensitization mechanisms contribute to the manifestation of IC/PBS, at least in some patients. Here we provide an overview of research efforts to characterize IC/BPS and evaluate therapies; when appropriate the possible limitations of this prior work are highlighted.A rationale for developing new strategies to address longstanding and fundamental questions for IC/BPS is also proposed and a number of research and clinical programs that have employed such novel approaches are cited. The importance of collaboration between IC/BPS-focused studies and wider research efforts to promote a more holistic understanding of this syndrome in the context of other urologic and non-urologic disorders is also stressed. These research directions are expected to foster new insights into IC/BPS that may inform future clinical studies and treatment. In this article we restrict our terminology to IC/BPS except in cases where the original reports used other nomenclature. Limitations of past approaches Numerous research studies and clinical trials of IC/BPS have been conducted since the early 1990’s to identify etiology, describe clinical course and risk factors, and identify effective therapies for this syndrome. Efforts to describe fundamental IC/BPS pathophysiology have addressed a broad set o.