Interstitial Cystitis/Painful Bladder Syndrome and Irritable Bowel Syndrome

间质性膀胱炎（1C）和肠易激综合征（IBS）影响15-30%的美国人口， 女性，其特征是慢性盆腔疼痛，泌尿和肠道症状重叠 功能障碍其病理生理学知之甚少。它们损害生活质量， 照顾负担。大多数患者对目前的治疗方法不满意。IBS和1C治疗失败，因为他们不 解决根本问题。我们的目标是研究引起1C和 IBS.我们对IBS的初步研究揭示了中枢和中枢神经系统内的适应不良的神经可塑性变化， 周围神经系统，但IC/IBS患者的骨盆底-脑神经肌肉轴尚未被发现。 考察我们假设在IC/IBS患者中，脑-骨盆底/肠道轴的双向信号紊乱， 患者我们将使用一种新的、非侵入性的、经过验证的研究大脑-骨盆底的方法来测试这一点 轴线 我们提出了四个具体的目标：1）检查过度兴奋的传入-骨盆底-脑轴， 通过对66例1C患者、66例1C合并IBS患者和30例健康对照者皮层诱发电位的测定， 电刺激直肠和肛门后的CEP和感觉阈值。2)研究 通过经颅磁刺激刺激皮质，记录传出脑-骨盆底轴， 肛门和直肠运动诱发电位（MEP）。3)确定神经元调制的位点，即 由于中枢或外周神经元致敏或两者引起的神经肠变化，通过唤起肛门和直肠 选择性刺激双侧腰骶神经后的MEP，并通过比较节段性 经颅诱发的MEP。4)通过评估IC/IBS患者出现肠道症状的原因， 肛门直肠感觉和感觉运动功能以及与肛门直肠相关的肠道和膀胱症状 超敏反应、直肠顺应性和骨盆底功能障碍。 我们的多学科综合方法将研究慢性脑缺血的神经生物学机制。 IC/IBS中的骨盆疼痛，以及它们与1C的区别。我们的研究将提供新的机制见解 关于这些重叠疼痛综合征的病理生物学，这可能对 我们对1C/IBS的理解，并为基于机制的治疗铺平道路。

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