Mechanisms of Central and Peripheral Hyperalgesia

中枢和外周痛觉过敏的机制

• 批准号: 6859663
• 负责人: George Nicholas Verne
• 金额: $ 31.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6859663
• 关键词: abdomen; adolescence (12-20); adult human (21+); behavioral /social science research tag; blood pressure; blood tests; clinical research; cold temperature; cortisol; endorphins; heart rate; heat stimulus; human subject; hyperalgesia; irritable bowel syndrome; ischemia; limbs; mechanical pressure; pain threshold; pathologic process; psychophysiology; psychosomatic disorders; questionnaires

DESCRIPTION (provided by applicant): Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel function (diarrhea and/or constipation). IBS is estimated to effect 20% of the United States population. Although the pathophysiology of IBS is unknown, visceral hypersensitivity (i.e., decreased pain thresholds in response to gut distension) is a clinical marker of the disorder present in the majority of patients with IBS. The mechanisms that lead to chronic visceral hypersensitivity, however, are currently unknown. Our laboratory has acquired evidence that patients with IBS also display somatic hypersensitivity in response to experimental thermal pain stimuli. These new findings differ from previous investigations that indicated IBS-associated hypersensitivity is limited to the gut. In contrast, our data suggest that IBS is characterized by more widespread alterations in central pain processing. Based on our preliminary data, we propose the novel, mechanistic hypothesis that IBS patients have a generalized but graded hypersensitivity to somatic nociceptive stimuli. We anticipate that this somatic hypersensitivity is somatotopically organized such that the lower dermatomes that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. Moreover, we propose that the hypersensitivity will be greater for deep, tonic stimuli than for superficial, brief stimuli. Importantly, no investigator to date has attempted to systematically characterize perceptual and physiological responses to multiple somatic pain stimuli among patients with IBS. Therefore, we propose the following specific aims. Specific Aim 1: To test for differences in somatic hypersensitivity between patients with IBS compared to controls across spatial areas that provide spinal input at differing levels. In order to accomplish this aim, we will assess perceptual responses to four well-validated experimental somatic pain stimuli (thermal pain, pressure pain, cold pressor pain, ischemic pain) across three body sites (forearm, abdomen, leg). Specific Aim 2: To test for differences between patients with IBS compared to controls as a function of the characteristics of the pain stimuli (deep vs. superficial, spatial area stimulated). Specific Aim 3: To characterize differences in physiological responses to experimental pain stimuli between IBS patients and controls and to examine contributions of physiological responses to pain perception. In order to accomplish this aim, we will assess cardiovascular and neuroendocrine responses to thermal, mechanical, cold pressor, and ischemic pain stimuli. Specific Aim 4: To establish the clinical relevance of somatic pain responses among IBS patients by determining whether responses to experimental pain stimuli predict variability in IBS patients' scores on the Functional Bowel Disorder Severity Index.

描述（由申请人提供）：肠易激综合症（IBS）是一种常见的胃肠道疾病，其特征是慢性腹痛和肠功能改变（腹泻和/或便秘）。据估计，IBS 影响着 20% 的美国人口。尽管 IBS 的病理生理学尚不清楚，但内脏过敏（即因肠道扩张而导致疼痛阈值降低）是大多数 IBS 患者存在的疾病的临床标志。然而，导致慢性内脏过敏的机制目前尚不清楚。 我们的实验室获得的证据表明，IBS 患者对实验性热痛刺激也表现出躯体超敏反应。这些新发现与之前的研究不同，之前的研究表明IBS相关的超敏反应仅限于肠道。相比之下，我们的数据表明IBS的特点是中枢疼痛处理发生更广泛的改变。根据我们的初步数据，我们提出了一种新颖的机制假设，即 IBS 患者对躯体伤害性刺激具有普遍但分级的超敏反应。我们预计这种躯体超敏反应是按体位组织的，因此与结肠共享内脏体汇聚的下皮区表现出最大的超敏反应。此外，我们认为对深层、强直刺激的超敏反应比对浅表、短暂刺激的超敏反应更大。重要的是，迄今为止还没有研究人员尝试系统地描述 IBS 患者对多种躯体疼痛刺激的知觉和生理反应。因此，我们提出以下具体目标。 具体目标 1：测试 IBS 患者与对照组之间在提供不同水平脊髓输入的空间区域中躯体超敏性的差异。为了实现这一目标，我们将评估三个身体部位（前臂、腹部、腿部）对四种经过充分验证的实验性躯体疼痛刺激（热痛、压力痛、冷压痛、缺血性痛）的知觉反应。 具体目标 2：测试 IBS 患者与对照组之间的差异，作为疼痛刺激特征（深部与浅部、刺激的空间区域）的函数。具体目标 3：表征 IBS 患者和对照组之间对实验性疼痛刺激的生理反应差异，并检查生理反应对疼痛感知的贡献。为了实现这一目标，我们将评估心血管和神经内分泌对热、机械、冷加压和缺血性疼痛刺激的反应。具体目标 4：通过确定对实验性疼痛刺激的反应是否可以预测 IBS 患者功能性肠病严重程度指数评分的变异性，确定 IBS 患者躯体疼痛反应的临床相关性。