Mechanism of Pain in Patients with Fibromyalgia Syndrome

描述：纤维肌痛综合征(FMS)是一种基于症状的诊断，依赖于慢性广泛性疼痛的存在和机械性疼痛阈值的降低，在&gt；=11个明确的压痛点。FMS显示出与其他疼痛综合征的广泛重叠，包括慢性疲劳综合征和肠易激综合征。所有这些疾病都有慢性的、无法解释的疼痛作为一种临床相关症状，并且这些症状中的几个或所有通常在单个患者中共存。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，包括第二次疼痛的过度暂时性总和(Wdup)和中枢敏化。通过这一应用，我们将扩展我们对与FMS疼痛相关的中枢/外周疼痛机制的详细研究，使用可靠地唤起对第二次疼痛的感知的重复刺激形式。第二痛是由外周C(无髓鞘)传入轴突的冲动传导引起的，第二痛的暂时性总和被证明是由背角内的中枢NMDA受体机制引起的。这些实验将评估外周对FMS疼痛的影响和实验疼痛的异常时间总和，将描述通过伤害性输入激活NMDA受体的中枢模式，并将比较NMDA拮抗剂对女性FMS患者和男性和女性对照组的临床和实验疼痛的影响。目的1重点探讨临床疼痛与FMS异常收缩(WU)的关系。由于报告的不同身体部位的临床疼痛强度似乎在FMS患者内部和之间差异很大，我们将首先测试FMS患者的所有四个身体象限的WU和临床疼痛评级的大小，然后从统计上确定它们之间的关联强度。重复的热刺激和机械刺激将提供给FMS患者和正常对照组(NC)。如果临床疼痛确实与C-传入调节机制有关，我们期望在WU测量和临床疼痛之间找到正相关。我们将使用运动或缺血性肌肉按压与休息交替进行的方式，研究肌肉骨骼伤害性感受器的输入在以下方面的作用：a)局部和全身性疼痛；b)FMS患者的Wu异常(AIM2)。我们期望发现肌肉活动和相关的受体刺激将增加局部和整体的临床疼痛。我们将测试NMDA受体拮抗剂对临床疼痛、第一疼痛、第二疼痛和吴(目标3)的影响。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促进FMS疼痛，特别是FMS相关差异。我们将使用功能性脑成像(FMRI)对NC和FMS患者的第二次疼痛进行时间总和，以表征皮质和皮质下结构中短暂、重复、热刺激的编码(目标4)。我们推测，与NC相比，FMS患者增强的WU将与更大的神经激活密切相关。建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，这些机制与FMS的诊断和治疗有关。此外，我们的发现可能有助于理解与其他慢性疼痛障碍相关的疼痛机制。

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.