Peripheral and Central Mechanism of Pain in Patients with Fibromyalgia

纤维肌痛患者疼痛的外周和中枢机制

基本信息

批准号：
7777306
负责人：
ROLAND STAUD
金额：
$ 30.56万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2012-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7777306
关键词：
Absence of pain sensation Accounting Age Analgesics Anesthesia procedures Area Chronic Chronic Fatigue Syndrome Chronic low back pain Classification Clinical Cutaneous Cutaneous Muscle Data Databases Distant Double-Blind Method Effectiveness Experimental Designs Fibromyalgia Funding Future General Population Gulf War Heating Hyperalgesia Injection of therapeutic agent Intervention Intramuscular Irritable Bowel Syndrome Lidocaine Local anesthesia Mandibular Diseases Measures Mechanics Methods Multiple Chemical Sensitivity Muscle Musculoskeletal Pain Myalgia Natural History Nociception Nociceptors Pain Pain Disorder Patients Peripheral Placebo Effect Placebos Play Price Primary Hyperalgesias Process Psychophysiology Relative (related person)Research Research Design Research Personnel Role Saline Secondary Hyperalgesias Sensory Source Stimulus Study Subject Suggestion Symptoms Syndrome Testing Therapeutic Effect Thermal Hyperalgesias Work base central pain chronic pain clinically relevant compare effectiveness design expectation mechanical allodynia mechanical pressure patient population population based pressure programs research study response sex spontaneous pain trapezius muscle

项目摘要

DESCRIPTION (provided by applicant): The Aim of this application is to characterize peripheral and central pain mechanisms relevant for clinical pain in subjects with fibromyalgia syndrome (FM). Because tonic nociceptive muscle input may play an important role for chronic pain and hyperalgesia in FM and other musculoskeletal pain syndromes, a careful psychophysical characterization of the response of FM subjects to muscle manipulations could provide crucial support of this hypothesis. The first Specific Aim of this application will characterize the mechanical and thermal hyperalgesia of FM and NC subjects in relation to carefully controlled tonic pain manipulation of muscles. We posit that local spontaneous pain in FM is strongly indicative of local and widespread thermal and mechanical hyperalgesia. In addition, we will test the role of experimental manipulations of peripheral tonic nociceptive input on clinical pain and local/widespread hyperalgesia of FM subjects by applying sustained mechanical pressure to tender muscles (tonic nociceptive input). We posit that clinical pain and cutaneous/muscle pain sensitivity will more markedly increase following tonic muscle stimulation in FM compared to NC subjects, and these effects will be particularly prolonged for FM subjects. We will compare the results of mechanical and thermal test stimuli obtained during baseline testing with those obtained after the muscle stimulation, An increase of adjacent and possibly of distant secondary hyperalgesia relative to the manipulated muscle area would support the role of tonic muscle nociceptive input for hyperalgesia and clinical pain of FM subjects. In the second Specific Aim we will study the analgesic mechanisms of FM subjects related to injections of lidocaine or saline placebo into painful trapezius muscle (TrapM) tender points (analgesia). We posit that local lidocaine/saline placebo injection into one TrapM tender point will have several effects; a) it will reduce muscle hyperalgesia (primary) and local pain after injection; b) it will reduce the secondary cutaneous hyperalgesia of FM subjects within adjacent and distant body areas; c) it will reduce general clinical FM pain. We will compare the response to thermal and mechanical test stimuli obtained during baseline testing with those obtained after the muscle injections. We will carefully estimate the contribution of the placebo effect by comparing the natural history (no analgesic intervention) to saline placebo and lidocaine injections during tonic painful muscle stimuli. Importantly, the study design will provide clinically relevant information about the relative contribution of peripheral analgesic mechanisms (i.e. anesthesia of peripheral sources of algesic input) and placebo analgesic mechanisms to local and general reductions in FM pain. We posit: a) Intramuscular lidocaine injections will produce larger reductions in local and generalized pain than will saline placebo injections and b) the variance in placebo responses will be strongly associated with ratings of expected pain intensities and desire for pain reduction, consistent with our previous work. Although it is possible that placebo factors alone are sufficient to produce reductions in both clinical pain and hyperalgesia and may account for some, most, or even all of the variance in therapeutic effects from muscle injections, our preliminary data showed superior effectiveness of lidocaine injections. Thus, such findings would be of considerable clinical and mechanistic significance, because they would corroborate previous work showing considerable effects of lidocaine on hyperalgesic states and provide estimates of their magnitude. In the third Specific Aim we will evaluate the placebo effects of analgesic manipulations (lidocaine or saline placebo) on experimental and clinical pain. We posit that a) manipulations designed to increase the placebo effect (verbal suggestions) will enhance the analgesic efficacy of lidocaine and saline injections; b) the magnitude of the placebo effect is predicted by expectations and desire for pain relief. Characterization of the placebo effect will provide important information on analgesic mechanisms related to muscle injections. Thus our application will not only provide strong evidence for or against the role of tonic nociceptive input from muscles as a relevant mechanism for clinical pain and hyperalgesia of FM patients but also delineate the analgesic mechanisms (central, peripheral, or both) that are operant during injections of painful muscles. Either way, we will provide evidence that will characterize the role of local anesthesia, placebo analgesia, or both. Thus patients with FM and other similar pain syndromes may strongly benefit from the results of our study.

描述（由申请人提供）：本申请的目的是表征与纤维肌痛综合征（FM）受试者的临床疼痛相关的外周和中枢疼痛机制。由于强直伤害性肌肉输入可能在 FM 和其他肌肉骨骼疼痛综合征中的慢性疼痛和痛觉过敏中发挥重要作用，因此对 FM 受试者对肌肉操作的反应进行仔细的心理物理表征可以为这一假设提供重要支持。该应用的第一个具体目标将表征 FM 和 NC 受试者与仔细控制的肌肉强直性疼痛操作相关的机械和热痛觉过敏。我们认为 FM 中的局部自发疼痛强烈表明局部和广泛的热和机械痛觉过敏。此外，我们将通过对嫩肌施加持续的机械压力（强直伤害性输入）来测试外周强直性伤害性输入的实验操作对 FM 受试者的临床疼痛和局部/广泛痛觉过敏的作用。我们认为，与 NC 受试者相比，FM 受试者在接受强直肌刺激后，临床疼痛和皮肤/肌肉疼痛敏感性将更显着增加，并且这些效应对于 FM 受试者将特别延长。我们将比较基线测试期间获得的机械和热测试刺激的结果与肌肉刺激后获得的结果，相对于被操纵的肌肉区域，邻近的和可能的远处继发性痛觉过敏的增加将支持强直性肌肉伤害性输入对痛觉过敏的作用。和 FM 受试者的临床疼痛。在第二个具体目标中，我们将研究与向疼痛的斜方肌 (TrapM) 压痛点注射利多卡因或生理盐水安慰剂相关的 FM 受试者的镇痛机制（镇痛）。我们假设将利多卡因/生理盐水安慰剂注射到一个 TrapM 压痛点会产生多种效果； a) 减少注射后肌肉痛觉过敏（原发性）和局部疼痛； b) 它将减少 FM 受试者在邻近和远处身体区域内的继发性皮肤痛觉过敏； c) 它将减轻一般临床 FM 疼痛。我们将比较基线测试期间获得的热和机械测试刺激的反应与肌肉注射后获得的反应。我们将通过比较生理盐水安慰剂和利多卡因注射在强直性疼痛肌肉刺激过程中的自然史（无镇痛干预）来仔细估计安慰剂效应的贡献。重要的是，研究设计将提供关于外周镇痛机制（即外周痛觉输入源的麻醉）和安慰剂镇痛机制对局部和全身 FM 疼痛减轻的相对贡献的临床相关信息。我们假设：a) 肌内注射利多卡因比注射生理盐水安慰剂更能减轻局部和全身疼痛，b) 安慰剂反应的差异将与预期疼痛强度的评级和减轻疼痛的愿望密切相关，这与我们之前的研究一致工作。尽管单独使用安慰剂因素可能足以减轻临床疼痛和痛觉过敏，并可能解释肌肉注射治疗效果的部分、大部分甚至全部差异，但我们的初步数据显示利多卡因注射具有卓越的有效性。因此，这些发现将具有相当大的临床和机制意义，因为它们将证实以前的工作，显示利多卡因对痛觉过敏状态有相当大的影响，并提供其程度的估计。在第三个具体目标中，我们将评估镇痛操作（利多卡因或生理盐水安慰剂）对实验和临床疼痛的安慰剂效应。我们假设 a) 旨在增加安慰剂效应（口头建议）的操作将增强利多卡因和盐水注射的镇痛功效； b) 安慰剂效应的大小是通过对缓解疼痛的期望和愿望来预测的。安慰剂效应的表征将为与肌肉注射相关的镇痛机制提供重要信息。因此，我们的应用不仅将为支持或反对来自肌肉的强直伤害性输入作为 FM 患者临床疼痛和痛觉过敏的相关机制的作用提供强有力的证据，而且还将描述在 FM 患者过程中起作用的镇痛机制（中枢、外周或两者）。注射疼痛的肌肉。无论哪种方式，我们都将提供证据来描述局部麻醉、安慰剂镇痛或两者的作用。因此，患有 FM 和其他类似疼痛综合征的患者可能会从我们的研究结果中受益匪浅。