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: 7193396
• 负责人: ROLAND STAUD
• 金额: $ 31.6万
• 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/7193396
• 关键词: Acute; Acute Pain; Affect; Animal Model; Anterior; Area; Attenuated; Axon; Brain; Brain imaging; C Fiber; Cerebrum; Chronic; Chronic Disease; Chronic Fatigue Syndrome; Clinical; Complex Regional Pain Syndromes; Condition; Cutaneous; D Aspartate; Data; Dextromethorphan; Diagnosis; Disease; Dose; Esthesia; Etiology; Exercise; Exertion; Fatigue; Female; Fiber; Fibromyalgia; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Heating; Hyperalgesia; Individual; Individual Differences; Infection; Insula of Reil; Investigation; Irritable Bowel Syndrome; Lead; Localized; Location; Lower Extremity; Magnetic Resonance Imaging; Maintenance; Measurement; Mechanics; Mediating; Metabolism; Modality; Modification; Muscle; Musculoskeletal; Musculoskeletal Pain; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; NMDA receptor antagonist; Neuraxis; Neurons; Nociception; Nociceptive Stimulus; Nociceptors; Organism; Pain; Pain Disorder; Pain Threshold; Pain-Free; Patient Self-Report; Patients; Pattern; Perception; Peripheral; Persistent pain; Personal Satisfaction; Physical activity; Population; Positron-Emission Tomography; Posterior Horn Cells; Prefrontal Cortex; Price; Principal Investigator; Process; Psychophysiology; Rate; Receptor Activation; Reporting; Research Personnel; Rest; Role; Secondary Hyperalgesias; Sensory; Serum; Site; Somatosensory Cortex; Source; Stimulus; Structure; Symptoms; Syndrome; System; Test Result; Testing; Thalamic structure; Therapeutic; Therapy Clinical Trials; Time; Trauma; United States; Upper arm; Visceral; Woman; allodynia; attenuation; base; central pain; central sensitization; chronic pain; chronic widespread pain; cingulate cortex; clinically relevant; design; dorsal horn; insight; male; mechanical pressure; novel diagnostics; pain inhibition; programs; receptive field; receptor; relating to nervous system; research study; response; sensory stimulus; soft tissue

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，取决于是否存在慢性广泛疼痛以及 >= 11 个明确定义的压痛点处机械痛阈值降低。 FMS 与其他疼痛综合征有广泛的重叠，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，并且这些综合征中的几种或全部通常在个体患者中共存。因此，FMS疼痛机制的发现也可能使患有相关疼痛综合征的患者受益。我们最近发现 FMS 患者表现出异常的疼痛处理，包括第二次疼痛（结束）和中枢敏化的过度时间总和。通过此应用，我们将使用可靠地唤起第二次疼痛感知的重复刺激形式，扩大对与 FMS 疼痛相关的中枢/外周疼痛机制的详细研究。第二次疼痛是由外周 C（无髓鞘）传入轴突的冲动传导引起的，第二次疼痛的时间总和已被证明是由背角内的中枢 NMDA 受体机制引起的。拟议的实验将评估 FMS 疼痛的外周影响和实验疼痛的异常时间总和，将描述伤害性输入引起的 NMDA 受体激活的中心模式，并将比较 NMDA 拮抗剂对女性 FMS 患者和男性和男性 FMS 患者临床和实验疼痛的影响。女性对照对象。目标 1 将重点关注 FMS 中临床疼痛与异常饱和 (WU) 的关系。由于 FMS 患者内部和之间报告的不同身体部位的临床疼痛强度似乎差异很大，因此我们将首先测试 FMS 患者所有四个身体象限的 WU 大小和临床疼痛评级，然后统计确定其关联强度。将向 FMS 患者和正常对照 (NC) 提供重复的热和机械刺激。如果临床疼痛确实与 C 传入介导的机制有关，我们预计会发现 WU 测量值与临床疼痛之间呈正相关。通过锻炼或缺血性肌肉压缩与休息时间交替，我们将描述肌肉骨骼伤害感受器输入对 FMS 患者的 a) 局部和全身疼痛和 b) WU 异常的作用 (目标 2)。我们期望发现肌肉活动和相关的受体刺激将增强局部和全身的临床疼痛。我们将测试 NMDA 受体拮抗剂对临床疼痛、首次疼痛、二次疼痛和 WU 的影响（目标 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 机制异常在多大程度上导致 FMS 疼痛，并特别关注 FMS 相关差异。我们将使用 NC 和 FMS 患者第二次疼痛时间总和的功能性脑成像 (fMRI) 来表征皮质和皮质下结构中短暂、重复、热刺激的编码（目标 4）。我们认为，与 NC 患者相比，FMS 患者 WU 的增强与更大的神经激活密切相关。拟议的实验将回答有关慢性疼痛的外周/中枢机制的重要问题，这些问题与 FMS 的诊断和治疗相关。此外，我们的研究结果可能有助于理解与其他慢性疼痛疾病相关的疼痛机制。