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: 2864101
• 负责人: ROLAND STAUD
• 金额: $ 18.31万
• 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 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2864101
• 关键词: C fiber; NMDA receptors; chronic pain; clinical research; dextromethorphan; drug screening /evaluation; endogenous opioid; exercise; fentanyl; fibromyalgia; gender difference; human subject; myelin; naloxone; oral administration; pain; pain threshold; psychopharmacology; psychophysics; sex hormones; somatic afferent nerve

Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain associated with allodynia. Our preliminary experiments with FMS subjects have indicated abnormalities of second pain in these patients which are related to central N-methyl-D-aspartate (NMDA) receptor processing. Our basic hypothesis is that abnormal central pain processing of second pain in FMS subjects is one of the fundamental abnormalities in this syndrome. Second pain results from impulse conduction in peripheral C (unmyelinated) afferent axons and is particularly sensitive to inhibition by opioid compounds. Second pain also increases in intensity when stimuli are applied more often than once every three seconds and this summation has been hypothesized to result from a central NMDA receptor mechanism. First pain is related to stimulation of A-Delta (myelinated) nociceptors and has been utilized almost exclusively to evaluate pain sensitivity. In order to compare directly abnormal processing of A-Delta and C-Fiber input in FMS subjects, we will utilize forms of brief experimental pain stimuli that can reliably evoke perceptions of first and second pain when applied to the hand or foot of human subjects. We will test the hypothesis that oral doses of dextromethorphan, a common cough suppressant and NMDA receptor antagonist, will selectively reduce temporal summation of second pain for normal male and female subjects. The purpose of another experiment is to examine the effects of graded doses of naloxone and fentanyl on first and second pain and temporal summation of second pain for normal male and female subjects, This analysis is designed to answer questions about opioid mechanisms of pain reduction and about the possible existence of a tonic endogenous pain modulatory system. These psychophysical tests of NMDA receptor mechanisms, opioid responsiveness, and level of tonic pain inhibitory mechanisms will then be compared across pain-free control subjects and fibromyalgia patients in order to ascertain the extent to which abnormalities of these mechanisms contribute to these pain states. Potential sex differences in pain sensitivity and effects of pharmacological manipulations will be evaluated in normal subjects and pain patients, with attention to the impact of psychosocial variables. Also, relevant to the greater risk factor for females to present with fibromyalgia, ovarian hormone states will be monitored in female subjects. Because fibromyalgia is a generalized muscular pain disorder which characteristically worsens with physical activity, the effects of exercise on different forms of pain sensitivity will be compared for fibromyalgia patients and matched normal controls.

纤维肌痛综合征（FMS）的特征是慢性疼痛与异常性疾病有关。 我们对FMS受试者进行的初步实验表明，这些患者的第二次疼痛异常与中央N-甲基-D-天冬氨酸（NMDA）受体处理有关。 我们的基本假设是，FMS受试者第二次疼痛的异常中心疼痛处理是该综合征的基本异常之一。 第二次疼痛是由于外围C（无髓鞘）传入轴突的冲动传导引起的，并且对阿片类化合物的抑制作用尤其敏感。当刺激的频率超过一次每三秒钟时，第二次疼痛也会增加强度，并且已经假设该总结是由中央NMDA受体机制导致的。 首先疼痛与刺激A-DELTA（髓鞘）伤害感受器有关，并且几乎完全用于评估疼痛敏感性。 为了比较FMS受试者中A-DELTA和C纤维输入的异常处理，我们将利用短暂的实验性疼痛刺激的形式，当应用于人类受试者的手或脚时，可以可靠地引起对第一和第二疼痛的看法。 我们将检验以下假设：右美甲肾剂量是一种常见的止咳药抑制剂和NMDA受体拮抗剂，将有选择地减少正常男性和女性受试者第二次疼痛的时间求和。 另一个实验的目的是检查纳洛酮和芬太尼的分级剂量对正常男性和女性受试者的第二次疼痛的时间刺激的影响，该分析旨在回答有关减轻疼痛的阿片类药物机制以及可能存在滋补性内源性疼痛调节系统的问题。 然后将在无疼痛的对照受试者和纤维肌痛患者中比较这些NMDA受体机制，阿片类药物反应性以及补品疼痛抑制机制水平的心理物理测试，以确定这些机制的异常程度对这些疼痛有助于这些状态。 在正常受试者和疼痛患者中，将评估疼痛敏感性的潜在性别差异以及药理学操纵的影响，并注意社会心理变量的影响。同样，与女性伴有纤维肌痛的更大危险因素有关，将监测女性受试者的卵巢激素状态。 由于纤维肌痛是一种普遍的肌肉疼痛障碍，其特征在于体育活动，因此将比较纤维肌痛患者的运动对不同形式的疼痛敏感性的影响并匹配正常对照。