INVESTIGATION OF ADENOSINE IN THE PATHOGENESIS OF NONCARDIAC CHEST PAIN

腺苷在非心源性胸痛发病机制中的研究

• 批准号: 7376990
• 负责人: Satish SC Rao
• 金额: $ 0.3万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376990
• 关键词: INVESTIGATION; ADENOSINE; PATHOGENESIS; NONCARDIAC; CHEST

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Each year in the United States more than 300,000 new patients receive a diagnosis of noncardiac chest pain (NCCP) and more than $1 billion is spent on their health care. Its pathophysiology is poorly understood and there is no approved treatment. These investigators' unique studies have established that visceral hyperalgesia is a key mechanism for NCCP and pain is independent of muscle dysfunction. Whether visceral hyperalgesia is a peripheral perturbation involving mechanoreceptors and afferent neurons or due to abnormal cortical processing is unclear. Whether there is coactivation of the emotional brain, anterior cingulate cortex (ACC) and thinking brain, pre frontal cortex (PFC) or dissocation between these two structures is not known. Also, the mediators for visceral hyperalgesia have not been characterized. Recently, we have shown that theophyllin (an adenosine receptor antagonist) increases the thresholds for pain in NCCP, suggesting a possible role for adenosine. This protocol will investigate the role of adenosine, visceral hyperalgesia and brain-visceral axis in the pathogenesis of NCCP. The specific aims are to investigate if healthy subjects (Aim 1) and patients with NCCP (Aim 2) who receive adenosine, when compared to those who receive placebo demonstrate a) lower thresholds for perception and pain during esophageal balloon distention and b) enhanced activation of PFC and ACC. Also, these investigators will investigate c) if patients demonstrate lower thresholds and greater cortical activation than controls. Aim 3: They hypothesize that pretreatment with theophyllin blocks the effects of adenosine on chest pain. Methods: The investigators will examine 20 healthy subjects and 20 patients with NCCP for testing Aims 1 and 2. Graded balloon distentions of the esophagus will be performed to assess perception and pain. Simultaneously, fMRI will be performed to assess cortical activity. Next, subjects will be randomized to receive either adenosine or placebo infusion and balloon distention and fMRI will be repeated. For testing Aim 3, they will examine 20 patients with NCCP. patients will be pretreated with either theophyllin or placebo. Next, balloon distention will be performed during infusion of adenosine. This interdisciplinary project should provide valuable mechanistic insights regarding the pathogenesis of NCCP, in particular the role of adenosine and the brain-visceral axis in mediating chest pain.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在美国，每年有超过30万名新患者被诊断为非心源性胸痛（NCCP），超过10亿美元用于他们的医疗保健。其病理生理学知之甚少，也没有批准的治疗方法。这些研究者的独特研究已经确定内脏痛觉过敏是NCCP的关键机制，并且疼痛独立于肌肉功能障碍。内脏痛觉过敏是否是一种涉及机械感受器和传入神经元的外周扰动，还是由于异常的皮层处理尚不清楚。情绪脑、前扣带皮层（ACC）和思维脑、前额叶皮层（PFC）是否存在共激活或这两个结构之间的分离尚不清楚。此外，内脏痛觉过敏的介质还没有得到表征。最近，我们已经表明，茶碱（腺苷受体拮抗剂）增加NCCP的疼痛阈值，这表明腺苷可能的作用。本研究将探讨腺苷、内脏痛觉过敏和脑-内脏轴在NCCP发病机制中的作用。具体目的是研究与接受安慰剂的受试者相比，接受腺苷的健康受试者（目的1）和NCCP患者（目的2）是否表现出a）食管球囊扩张期间感知和疼痛阈值降低和B）PFC和ACC激活增强。此外，这些研究者还将研究c）患者是否表现出阈值降低和皮质激活增强。目的3：他们假设预先用茶碱阻断腺苷对胸痛的作用。方法：研究者将检测20名健康受试者和20名NCCP患者，以测试目的1和2。将对食管进行分级球囊扩张，以评估感知和疼痛。同时，将进行fMRI以评估皮质活动。接下来，受试者将随机接受腺苷或安慰剂输注，并重复球囊扩张和fMRI。为了测试目标3，他们将检查20名NCCP患者。患者将用茶碱或安慰剂进行预治疗。接下来，在输注腺苷期间进行球囊扩张。这个跨学科的项目应该提供有价值的机制的见解，关于NCCP的发病机制，特别是腺苷和脑内脏轴在介导胸痛的作用。