Investigation and treatment of central nervous system dysfunction in chronic pelv

慢性盆腔炎中枢神经系统功能障碍的调查与治疗

• 批准号: 7739882
• 负责人: Felipe Fregni
• 金额: $ 0.53万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2009-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739882
• 关键词: Abdomen; Absenteeism; Accounting; Activities of Daily Living; Address; Aftercare; Amygdaloid structure; Analgesics; Anterior; Anti Inflammatory Analgesics; Anxiety; Area; Asthma; Back Pain; Biological Neural Networks; Brain; Chronic; Clinical; Cognitive; Cutaneous; Data; Disease; Double-Blind Method; Facilities and Administrative Costs; Functional disorder; Funding; Generations; Glutamates; Grant; Hand; Healthcare; High Prevalence; Hippocampus (Brain); Hyperactive behavior; Hyperalgesia; Inflammation; Injury; Intake; Interstitial Cystitis; Intervention; Investigation; Light; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mechanics; Medical; Methods; Muscle relaxants; Neuraxis; Neurons; Neurotransmitters; Operative Surgical Procedures; Organ; Pain; Pain Threshold; Pancreatitis; Pathway interactions; Patients; Pelvic Pain; Perception; Performance; Peripheral; Phase; Pilot Projects; Placebos; Prevalence; Process; Productivity; Protocols documentation; Quality of life; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Refractory; Reporting; Role; Safety; Sensory; Somatosensory Cortex; Structure; Symptoms; Techniques; Testing; Thalamic Nuclei; Visceral pain; Visual Analogue Pain Scale; Woman; Work; allodynia; base; central sensitization; chronic pancreatitis; chronic pelvic pain; cingulate cortex; cingulate gyrus; cohort; comparative efficacy; cutaneous allodynia; depression; indexing; insight; neurocognitive test; neuroimaging; neuromechanism; novel; novel therapeutic intervention; painful bladder syndrome; public health relevance; relating to nervous system; repetitive transcranial magnetic stimulation; response; tool

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.

描述（由申请人提供）：该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）——针对这种情况的可能的新颖治疗方法。这项研究很重要，因为慢性盆腔疼痛会对日常生活活动和总体健康产生相当大的影响，从而导致焦虑和抑郁。此外，这种疾病的患病率也相对较高——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难以通过药物和外科手术治疗，并且最近的证据表明中枢神经系统功能障碍（例如边缘区域（前扣带皮层））与慢性盆腔疼痛有关，因此我们假设慢性盆腔疼痛的病理生理学与慢性盆腔疼痛有关。与疼痛相关的神经网络活动异常。这一假设基于我们的试点数据，该数据显示无创脑刺激 (tDCS) 可显着减轻这些患者的疼痛，同时也基于我们 NIDDK-R03 资助的研究，其中我们表明另一种无创脑刺激技术可减轻慢性内脏疼痛。在这些患者中发现了胰腺炎引起的疼痛以及与疼痛相关的神经网络（如磁共振波谱索引）的变化。具体来说，我们将通过一项 II 期、双盲、假对照、平行、随机临床试验，研究 tDCS 在减轻一组慢性盆腔疼痛患者（患有膀胱疼痛综合征或间质性膀胱炎）疼痛方面的功效。通过一系列神经认知测试评估这种干预的安全性。此外，我们将评估这种治疗对异常性疼痛和痛觉过敏现象的影响，这些现象被认为是中枢敏化的替代物。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，该技术可以以无创且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过度活跃。这项研究的结果可能代表着建立慢性盆腔疼痛新治疗方法的重要一步，也将揭示其病理生理学。公共健康相关性：慢性盆腔疼痛会导致生活质量下降，直接年度医疗费用超过 28 亿美元，并会产生与缺勤、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、使人衰弱的疾病的患者通常对当前的药物治疗无效。因此，我们建议研究一种使用非侵入性脑刺激的新型治疗干预措施，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。