Neurophysiologic & Autonomic Characterization of Interstitial Cystitis/Painful Bl

描述（由申请人提供）：间质性膀胱炎/膀胱疼痛综合征（IC/PBS）是一种常见的慢性特发性内脏疼痛综合征（约占人口的2.5%），会产生严重的疼痛，并使处于生命黄金时期的年轻女性残疾。虽然IC/PBS历来从泌尿学角度被概念化，但膀胱壁异常的发现并没有导致有效的治疗。此外，IC/PBS的症状提示膀胱神经支配受损，包括感觉传入神经和自主传入神经。大量与IC/PBS相关的自主神经疾病在流行病学和临床上支持了这一重新概念，并提示存在更广泛和更远的核心缺陷。我们的长期目标是确定IC/PBS的广泛神经、心理和内分泌表型。我们假设IC/PBS实际上是一个更大的疾病家族的成员，该家族具有对压力、疼痛或威胁的异常中枢自主神经和感觉反应的共同（家族性？）易感性，通常在急性创伤事件（感染、损伤）后首次表现出来。这一假说预测，对IC/PBS患者及其家庭成员的仔细调查将揭示健康对照组中不存在的特定神经缺陷。通过与没有IC/PBS的肌筋膜盆腔疼痛患者的结果进行比较，特别强调与IC/PBS特异性相关的发现与非特异性慢性盆腔疼痛的区别。我们建议通过调查神经-泌尿、妇科、自主神经、胃肠和心理功能、早期不良经历的暴露以及这四组的应激反应系统的功能来验证这一创新假设。这项研究非常重要，因为它将首次为IC/PBS患者的中枢、外周、传入和传出神经系统功能提供详细的临床研究。不仅与健康受试者进行比较，而且与没有IC/PBS的慢性盆腔疼痛受试者进行比较，对于区分与疼痛存在相关的发现和与IC/PBS真正相关的发现至关重要。这一扩展的观点旨在更好地理解导致疾病过程的因果因素，并提出新的治疗或预防策略。公共卫生相关性：间质性膀胱炎/膀胱疼痛综合征（IC/PBS）在一大批处于生育期的年轻女性中引起严重的膀胱疼痛和广泛的残疾。对膀胱本身的广泛研究发现了许多异常，但我们不知道这些是疾病的原因还是结果。到目前为止，这些都没有在治疗方面取得任何真正的长期进展。我们发现，其他自主神经障碍经常发生在IC/PBS患者本身和患者的家庭成员中。因此，我们建议确定IC/PBS的主要异常是否实际上存在于自主神经系统，而不是膀胱。我们将通过仔细测量IC/PBS患者的自主神经功能和感觉来做到这一点，包括休息和控制心理压力。我们将与肌筋膜盆腔疼痛患者的测量结果进行比较，以了解哪些异常与IC/PBS真正相关，哪些只是反映盆腔疼痛的存在。

DESCRIPTION (provided by applicant): 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.