Interstitial cystitis (1C) and Irritable bowel syndrome (IBS) affect 15-30% of the US population, invariablywomen, and are characterized by overlapping symptoms of chronic pelvic pain, urinary and boweldysfunction. Their pathophysiology is poorly understood. They impair quality of life and impose major healthcare burden. Most patients are dissatisfied with current therapies. IBS & 1C therapy fail because they do notremedy the underlying problem. Our goal is to investigate the neurobiologic mechanisms that cause 1C andIBS. Our preliminary studies in IBS reveal maladaptive neuroplastic changes within the central andperipheral nervous system, but the pelvic floor-brain neuromuscular axis in IC/IBS patients has not beenexamined. We hypothesize that bidirectional signaling in the brain-pelvic floor/gut axis is deranged in IC/IBSpatients. We will test this by using a new, noninvasive and validated method of studying the brain-pelvic flooraxis.We propose four specific aims: 1) Examine the hyperexcitability of the afferent-pelvic floor-brain axis in66 patients with 1C, 66 patients with 1C and IBS and 30 healthy controls by measuring the cortical evokedpotentials (CEP) and sensory thresholds after electrical stimulation of the rectum and anus. 2) Study theefferent brain-pelvic floor axis by stimulating the cortex with transcranial magnetic stimulation and record theanal and rectal motor evoked potentials (MEP). 3) Determine the locus for neuronal modulation i.e are theneuroenteric changes due to central or peripheral neuronal sensitization or both, by evoking anal and rectalMEPs after selectively stimulating the lumbar and sacral nerves bilaterally, and by comparing segmental withtranscranial-induced MEPs. 4) Evaluate why IC/IBS patients experience bowel symptoms by assessinganorectal sensation and sensori-motor function and correlating bowel and bladder symptoms with anorectalhypersensitivity, rectal compliance and pelvic floor dysfunction.Our multidisciplinary, comprehensive approach will investigate the neurobiologic mechanisms of chronicpelvic pain in IC/IBS, and how they differ from 1C. Our studies will provide novel mechanistic insightsregarding the pathobiology of these overlapping pain syndromes, which could have a significant impact onour understanding of 1C/IBS, and pave the way for mechanistic-based therapies.
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