Interstitial Cystitis: Elucidation of the Psychophysiologic and Autonomic Characteristics (ICEPAC) Study

Overview

Interstitial cystitis/painful bladder syndrome (IC/PBS) causes severe bladder pain and extensive disability in a large group of women int he prime of their productive lives. Extensive study of the bladder itself has uncovered many abnormalities, but the investigators do not know if these are the cause or result of the disorder. None of these has led to any real long-term progress in treatment, so far. The investigators have found that other autonomic disorders often occur in both the patients themselves and in the family members of patients with IC/PBS. The investigators therefore propose to determine whether the main abnormality in IC/PBS actually lies in the autonomic nervous system, rather than the bladder. The investigators 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. The investigators will compare their 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.

The investigators primary hypothesis is that IC/PBS is a member of a larger family of disorders sharing aberrant central autonomic and sensory response to stress, pain or threat. These disorders appear to share a common vulnerability that seems to be conferred during development, and symptoms of these disorders usually are first manifested in response to an environmental trigger. This proposal aims to compare the neural, psychological, and endocrine phenotypes that characterize patients with IC/PBS with those of patients suffering myofascial pelvic pain (MPP) syndrome, an chronic pelvic pain distinct from IC/PBS, age-matched, healthy controls, and first degree relatives. These studies are designed to identify which levels of the neuraxis are impaired, both in the basal state, and in response to a well-characterized psychosocial stressor. Aim 1: To differentiate the specific baseline neurophysiological abnormalities that occur in IC/PBS from those present in patients with MPP and healthy subjects, specifically: 1a: Bladder and pelvic floor afferent and efferent urogynecological function: (1) voiding diaries (efferent) modified to include void-state related numeric rating scales for pain (afferent); Uroflow measurements (efferent), and a double-blind placebo-controlled evaluation of the diagnostic lidocaine instillation test (afferent) with impact on voiding function (efferent); (2) semi-quantitative evaluation of pelvic floor function and identification of myofascial trigger points (efferent), including inter-observer validation of a standardized semi-quantitative examination (afferent); (3) quantitative Q-tip test for vulvodynia (afferent) (4) evaluation of dysmenorrhea (afferent) and menstrual function (efferent). 1b: somatic afferent and autonomic efferent neural function, specifically: (1) global screen for autonomic and neurological abnormalities through the established Small Fiber Score Instrument (SFIBS) questionnaire and structured neurological examination (afferent and efferent); (2) specific evaluation of sacral and lumbar nerve root function through a focused neurological examination (afferent and efferent); (3) parasympathetic cardiac function through the cardiac response to deep breathing (efferent); (4) sympathetic cardiac and vasomotor functions through the cardiovascular responses to the Valsalva maneuver and to an upright tilt table test (efferent); (5) sudomotor sympathetic function through the quantitative sudomotor axon reflex test (QSART) that evaluates post-ganglionic function (specifically abnormal in autonomic neuropathies) and through a thermoregulatory sweat test (efferent). 1. c: gastrointestinal afferent and efferent function, specifically upper bowel motility with established methods: (1) early satiety \& gastric compliance by water load test (afferent). (2) gastric electrical activity through electrogastrography (efferent). Aim 2: To determine the specific developmental, psychiatric, pain, autonomic, and stress response characteristics common to IC/PBS and their family members, that differ from MPP and healthy subjects through: 2. a: Stress and trauma history in early childhood and adulthood. 2b: Psychiatric screening and psychometric quantitation of psychological symptoms, pain and function. 2c: Quantitation of associated co-morbid autonomic disorders through the ODYSA questionnaire. 2d: Salivary cortisol levels immediately prior to autonomic testing (anticipatory stress) and after a period of relaxation once the test is finished, in conjunction with a stress self-assessment inventory. 2e: Performance of the Trier test on a subset of patients and controls, with measurement of autonomic cardiovascular parameters, body temperature, catecholamine concentrations (norepinephrine, epinephrine, dopamine) and endocrine parameters: ACTH and adrenocortical hormones.