Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) is a chronic idiopathic visceral pain syndrome that occurs commonly (about 2.5% of the population), produces severe pain, and disables young women in the prime of their lives. Although IC/PBS has historically been conceptualized from a urologic perspective, the finding of bladder wall abnormalities has not led to effective treatment. Further, the symptoms of IC/PBS suggest impairment of bladder innervation, both sensory afferent and autonomic efferent. The large number of autonomic disorders epidemiologically and clinically associated with IC/PBS, support this reconceptualization and suggest a more widespread and remote core defect. Our long-term aim is to define the broad neural, psychological, and endocrine phenotypes that characterize IC/PBS. We hypothesize that IC/PBS actually is a member of a larger family of disorders that share a common (familial?) predisposition to aberrant central autonomic and sensory responses to stress, pain or threat, usually first manifested following an acute traumatic event (infection, injury). This hypothesis predicts that careful investigation of patients with IC/PBS and their family members will reveal specific neural defects that are not present in healthy controls. Special emphasis will also be placed on distinguishing findings that are specifically associated with IC/PBS, in contrast to non-specific chronic pelvic pain, by comparing the findings to those in patients with myofascial pelvic pain without IC/PBS. We propose to test this innovative hypothesis by investigating neuro-urologic, gynecologic, autonomic, gastrointestinal, and psychological function, exposure to early adverse experience, and function of the stress response system in each of these four groups,. This research is important because it will provide, for the first time, a detailed clinical investigation of central, peripheral, afferent and efferent nervous system function in many systems in addition to the bladder in patients with IC/PBS. The comparison with not only healthy subjects, but also subjects who have chronic pelvic pain without IC/PBS will be crucial to sort between findings related simply to the presence of pain, and those truly related to IC/PBS. This expanded view is designed to lead to a better understanding of causal factors that contribute to the disease process, and to suggest novel treatment or prevention strategies. PUBLIC HEALTH RELEVANCE: Interstitial cystitis/painful bladder syndrome (IC/PBS) causes severe bladder pain and extensive disability in a large group of young women in the prime of their productive lives. Extensive study of the bladder itself has uncovered many abnormalities, but we do not know if these are a cause or a result of the disorder. None of these has led to any real long-term progress in treatment, so far. We have found that other autonomic disorders often occur in both the patients themselves and in the family members of patients with IC/PBS. We therefore propose to determine whether the main abnormality in IC/PBS actually lies in the autonomic nervous system, rather than the bladder. We will do this through careful measurements of autonomic function and sensation in patients who have IC/PBS, both at rest, and under controlled psychological stress. We will compare our measurements to patients with myofascial pelvic pain, to know which abnormalities are truly linked to IC/PBS, and which simply reflect the presence of pelvic pain.