Mechanism of Pain in Patients with Fibromyalgia Syndrome

纤维肌痛综合征患者的疼痛机制

• 批准号: 6867378
• 负责人: ROLAND STAUD
• 金额: $ 33.12万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6867378
• 关键词: C fiber; NMDA receptors; chronic pain; cingulate gyrus; clinical research; dextromethorphan; dorsal horn; fibromyalgia; functional magnetic resonance imaging; gender difference; human subject; inhibitor /antagonist; myelin; nociceptin; pain; pain threshold; positron emission tomography; prefrontal lobe /cortex; psychophysics; somatic afferent nerve; thalamus

DESCRIPTION: Fibromyalgia syndrome (FMS) is a symptom based diagnosis that depends on the presence of chronic widespread pain and decreased mechanical pain threshold at >= 11 well defined tender points. FMS shows wide overlap with other pain syndromes, including chronic fatigue syndrome and irritable bowel syndrome. All these disorders share chronic, unexplained pain as a clinically relevant symptom and several or all of these syndromes often coexist in an individual patient. Therefore, discovery of FMS pain mechanisms may also benefit patients with related pain syndromes. We have recently shown that FMS patients demonstrate abnormal pain processing, including excessive temporal summation of second pain (windup) and central sensitization. With this application, we will expand our detailed investigation of central/peripheral pain mechanism relevant to FMS pain, using forms of repetitive stimulation that reliably evoke perceptions of second pain. Second pain results from impulse conduction in peripheral C (unmyelinated) afferent axons, and temporal summation of second pain has been shown to result from a central NMDA receptor mechanism within the dorsal horn. The proposed experiments will evaluate peripheral influences on FMS pain and abnormal temporal summation of experimental pain, will describe the central patterns of NMDA receptor activation by nociceptive input, and will compare effects of NMDA antagonists on clinical and experimental pain of female FMS patients and male and female control subjects. Aim 1 will focus on the relationship of clinical pain to abnormal windup (WU) in FMS. Since clinical pain intensities reported for different body areas seem to vary widely within and between FMS patients, we will first test the magnitude of WU and clinical pain ratings in all four body quadrants of FMS patients and then statistically determine the strength of their association. Repetitive thermal and mechanical stimuli will be delivered to FMS patients and normal controls (NC). If clinical pain is indeed related to C-afferent mediated mechanisms we expect to find a positive correlation between WU measurements and clinical pain. Using exercise bouts or ischemic muscle compressions alternating with rest periods, we will characterize the role of musculoskeletal nociceptor input on a) local and generalized pain and b) WU abnormalities of FMS patients (Aim2). We expect to find that muscular activity and associated receptor stimulation will enhance clinical pain both locally and generally. We will test the effects of NMDA receptor antagonists on clinical pain, first pain, second pain, and WU (Aim 3). We will compare the psychophysical test results across pain-free NC and FMS patients in order to ascertain the extent to which abnormalities of NMDA mechanisms contribute to FMS pain with a special focus on FMS related differences. We will use functional brain imaging (fMRI) of temporal summation of second pain in NC and FMS patients to characterize the encoding of brief, repetitive, thermal stimuli in cortical and subcortical structures (Aim 4). We posit that the enhanced WU of FMS patients will strongly correlate with greater neural activation as compared to NC. The proposed experiments will answer important questions about peripheral/central mechanisms of chronic pain that are relevant to the diagnosis and treatment of FMS. In addition, our findings may contribute to the understanding of pain mechanisms related to other chronic pain disorders.

描述：纤维肌痛综合征（FMS）是一种基于症状的诊断，取决于慢性广泛疼痛和机械疼痛阈值的存在，> = 11> = 11个明确定义的招标点。 FMS显示出与其他疼痛综合症的重叠，包括慢性疲劳综合征和肠易激综合征。所有这些疾病都具有慢性，无法解释的疼痛作为临床相关症状，并且这些综合症中的几种或所有这些综合症经常在单个患者中共存。因此，发现FMS疼痛机制也可能使患有相关疼痛综合征的患者受益。我们最近表明，FMS患者表现出异常的疼痛处理，包括第二次疼痛（Windup）和中枢敏化的时间求和。通过此应用，我们将使用重复刺激的形式来扩大对与FMS疼痛相关的中枢/外周疼痛机制的详细研究，这些刺激可可靠地引起对第二次疼痛的看法。第二次疼痛是由于外围C（无髓鞘）传递轴突的冲动传导引起的，第二次疼痛的时间求和已证明是由背角中的中央NMDA受体机制引起的。所提出的实验将评估对FMS疼痛的外周影响和实验性疼痛的异常时间求和，将描述伤害感受性输入的NMDA受体激活的中心模式，并将比较NMDA拮抗剂对女性FMS患者以及男性和女性FMS患者以及男性和女性对照受试者临床和实验性疼痛的影响。 AIM 1将重点放在FMS中临床疼痛与异常呼吸的关系上。由于在FMS患者之间和在FMS患者之间的临床疼痛强度似乎差异很大，因此我们将首先测试FMS患者所有四个体象限的WU和临床疼痛等级的大小，然后在统计上确定其关联的强度。重复的热和机械刺激将交付给FMS患者和正常对照（NC）。如果临床疼痛确实与C型介导的机制有关，我们希望在WU测量和临床疼痛之间找到正相关。我们将使用与休息期交替的运动次数或缺血性肌肉压缩，表征肌肉骨骼伤害感受器在a）局部和普遍性疼痛以及b）FMS患者的WU异常（AIM2）的作用（AIM2）。我们希望发现肌肉活动和相关的受体刺激将增强本地和一般的临床疼痛。我们将测试NMDA受体拮抗剂对临床疼痛，第一次疼痛，第二次疼痛和WU的影响（AIM 3）。我们将比较无痛NC和FMS患者的心理物理测试结果，以确定NMDA机制异常导致FMS疼痛的程度，特别关注与FMS相关的差异。我们将使用NC和FMS患者第二次疼痛的时间概括的功能性脑成像（fMRI）来表征皮质和皮质下结构中简短，重复的热刺激的编码（AIM 4）。我们认为，与NC相比，FMS患者的WU增强将与更大的神经激活密切相关。提出的实验将回答有关与FMS诊断和治疗有关的慢性疼痛外围/中心机制的重要问题。此外，我们的发现可能有助于理解与其他慢性疼痛障碍有关的疼痛机制。