Pain and Interstitial Cystitis

描述（由申请人提供）：间质性膀胱炎（IC）是一种慢性膀胱疾病，以尿频/尿急和耻骨上疼痛为特征。目前还没有持续有效的治疗方法。本研究的长期目标是更好地了解IC疼痛方面的病理生理机制，以便制定改进的治疗策略。临床、免疫学和神经生物学特征都支持IC是一种异质性综合征的假设。拟议的研究基于两个临床观察：首先，IC与其他慢性内脏疼痛综合征有许多共同特征。此外，许多IC患者报告膀胱外疼痛症状，如胃肠道、盆腔和慢性躯体疼痛。这一临床印象已得到一系列流行病学研究的证实。这些观察结果表明，IC的疼痛调节机制可能存在普遍的改变。其次，IC主要影响育龄妇女。这一观察结果表明，IC中伤害性加工的改变可能进一步受到性激素环境的调节。该建议的工作假设是：(1)一系列不同的损伤可导致IC患者的慢性疼痛，(2)不同的潜在致病性疼痛机制可能需要不同的治疗策略，(3)同一患者可能存在多种不同的致病性疼痛机制。目的1：我们建议使用神经生理学（伤害感觉功能的测量）、自主神经和心理参数、膀胱上皮功能的尿液标记物和细胞因子谱（尿液、血液）来详细描述IC患者的特征。目的2：我们将确定性激素环境对IC女性疾病症状的影响。我们希望根据测试的参数将IC患者区分为不同的亚组。这些研究的结果应该具有快速的临床意义：如果能够确定不同IC病因的患者亚群，那么他们就可以成为重点研究和特定治疗的目标。

DESCRIPTION (provided by applicant): Interstitial cystitis (IC) is a chronic bladder disease characterized by urinary frequency/urgency and suprapubic pain. There are currently no consistently effective treatments for IC available. The long-range objective of this research is to develop a better understanding of the pathophysiological mechanisms of the pain aspects of IC, in order to develop improved treatment strategies. Clinical, immunologic and neurobiologic characteristics all support the hypothesis that IC is a heterogeneous syndrome. The proposed studies are based on two clinical observations: First, IC shares many characteristics with other chronic visceral pain syndromes. In addition, many patients with IC report extra-bladder pain symptoms, such as gastrointestinal, pelvic and chronic somatic pain. This clinical impression has been confirmed by a series of epidemiological studies. These observations suggest that there might be generalized alterations in pain modulatory mechanisms in IC. Second, IC affects predominantly women in their reproductive ages. This observation suggests that the proposed alterations in nociceptive processing in IC might be further modulated by the gonadal hormonal milieu. The working hypotheses for this proposal are that (1) a spectrum of different insults can lead to chronic pain in patients suffering from IC, (2) different underlying pathogenic pain mechanisms may require different treatment strategies for patients diagnosed with IC, (3) multiple different pathogenic pain mechanisms may coexist in the same patient. The following aims address these hypotheses: Aim 1: We propose to characterize patients with IC in detail using neurophysiological (measures of nociceptive function), autonomic and psychological parameters, urine markers of bladder epithelial function and cytokine profiles (urine, blood). Aim 2: We will determine the influence of the gonadal hormonal milieu on symptoms of the disease in women with IC. We expect that patients with IC can be differentiated into distinct sub-groups, based on the parameters tested. The results of these studies should have rapid clinical implications: if subsets of patients with different IC etiologies can be identified, then they can be targeted for focused research and specific treatments.