Investigation and treatment of central nervous system dysfunction in chronic pelv

描述（由申请人提供）：本方案的目的是研究与慢性盆腔疼痛相关的中枢神经系统功能障碍，以及使用神经调节工具-经颅直流电刺激（tDCS）治疗这种疾病的可能的新治疗方法。这项研究很重要，因为慢性盆腔疼痛会对日常生活活动和整体健康产生相当大的影响，从而导致焦虑和抑郁。此外，这种疾病的患病率相对较高——美国女性慢性盆腔疼痛的患病率为3.7%，与哮喘（3.8%）和背痛（4.1%）等其他慢性疾病的患病率相当。由于慢性盆腔疼痛通常对医学和外科治疗是难治性的，最近的证据表明，慢性盆腔疼痛的中枢神经系统功能障碍，如边缘区（前扣带皮层），我们假设慢性盆腔疼痛的病理生理与疼痛相关神经网络的异常活动有关。这一假设是基于我们的试验数据，该数据显示非侵入性脑刺激（tDCS）可以显著减轻这些患者的疼痛，也基于我们的NIDDK-R03资助的研究，我们发现另一种非侵入性脑刺激技术可以减轻胰腺炎引起的慢性内脏疼痛，并且在这些患者中发现疼痛相关神经网络的变化（通过磁共振波谱索引）。具体来说，我们将通过一项ii期、双盲、假对照、平行、随机的临床试验，研究tDCS在减轻慢性盆腔疼痛患者（伴有膀胱疼痛综合征或间质性膀胱炎）疼痛方面的疗效，并通过一系列神经认知测试评估这种干预措施的安全性。此外，我们将评估这种治疗对异常性痛觉和痛觉过敏现象的影响，这些现象被认为是中枢致敏的替代品。最后，我们将使用磁共振波谱技术来研究这些患者的中枢神经功能障碍，磁共振波谱技术可以以无创和可靠的方式测量大脑代谢物。我们假设我们提出的干预措施将减少这些患者前扣带回的病理性亢进。本研究的结果可能是建立慢性盆腔疼痛新治疗方法的重要一步，也将阐明其病理生理学。公共卫生相关性：慢性盆腔疼痛导致生活质量下降，每年直接医疗费用超过28亿美元，并与旷工、生产力下降和工作表现障碍相关的间接成本。患有这种痛苦、虚弱的疾病的患者通常对目前的药物治疗难以治愈。因此，我们建议研究一种新的治疗干预方法，使用无创脑刺激，此外，使用磁共振成像研究这种疾病的神经基础-因此，这项研究的结果将为理解慢性盆腔疼痛的病理生理学提供见解。

DESCRIPTION (provided by applicant): The purpose of this protocol is to investigate the central nervous system dysfunction that is associated with chronic pelvic pain and also a possible novel treatment using a neuromodulatory tool - transcranial direct current stimulation (tDCS) - for this condition. This study is important as chronic pelvic pain can have a considerable impact in terms of interference with daily life activities and general well being which results in anxiety and depression. In addition, this condition has a relatively high prevalence - the prevalence rate of chronic pelvic pain in women in US is 3.7%, comparable with the numbers for other chronic conditions such as asthma (3.8%) and back pain (4.1%). Because chronic pelvic pain is often refractory to medical and surgical procedures and recent evidence suggests a central nervous system dysfunction - such as in the limbic areas (anterior cingulate cortex) - in chronic pelvic pain, we hypothesize that the pathophysiology of chronic pelvic pain is associated with abnormal activity in pain-related neural networks. This hypothesis is based on our pilot data showing that noninvasive brain stimulation (tDCS) induces a significant reduction in pain in these patients and also on our NIDDK-R03 funded study in which we showed that another technique of noninvasive brain stimulation reduces pain in chronic visceral pain due to pancreatitis and that changes in pain-related neural networks (as indexed by magnetic resonance spectroscopy) are found in these patients. Specifically, we will investigate the efficacy of tDCS in reducing pain in a cohort of chronic pelvic pain patients (with painful bladder syndrome or interstitial cystitis) via a phase-II, double-blinded, sham- controlled, parallel, randomized clinical trial and also assess the safety of this intervention via a battery of neurocognitive tests. Furthermore we will assess the impact of this treatment on the phenomenon of allodynia and hyperalgesia, which are known to be surrogates of central sensitization. Finally we will investigate the central neural dysfunction in these patients using the technique of magnetic resonance spectroscopy that can measure brain metabolites in a noninvasive and reliable manner. We hypothesize that our proposed intervention will reduce the pathological hyperactivity in the anterior cingulate gyrus in these patients. The results of this study may represent an important step for establishing a novel therapeutic approach for chronic pelvic pain and will also shed light on its pathophysiology. PUBLIC HEALTH RELEVANCE: Chronic pelvic pain results in a reduced quality of life, accounts for more than $2.8 billion dollars in direct annual healthcare expenses, and has indirect costs associated with absenteeism, reduced productivity, and hindered performance while at work. Patients who suffer from this painful, debilitating condition are often refractory to current pharmacological therapies. We therefore propose to investigate a novel therapeutic intervention using noninvasive brain stimulation and, in addition, investigate the neural basis of this disorder using magnetic resonance imaging - the results of this study will therefore provide insights into understanding the pathophysiology of chronic pelvic pain.