Phenotyping Evoked Central Sensitivity to Painful Stimuli

表型诱发中枢对疼痛刺激的敏感性

• 批准号: 8700651
• 负责人: Laura A Frey Law
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700651
• 关键词: Address; Adult; Affect; American; Ankle; Brain Injuries; Chronic; Clinical; Cluster Analysis; Complex; Data; Development; Diabetes Mellitus; Disinhibition; Equilibrium; Experimental Models; Future; Goals; Heart Diseases; Heating; Heterogeneity; Human; Hyperalgesia; Individual; Infusion procedures; Institute of Medicine (U.S.); Intramuscular; Knowledge; Link; Logistic Regressions; Malignant Neoplasms; Measurement; Measures; Mediating; Modality; Modeling; Musculoskeletal; Musculoskeletal Pain; Myalgia; Neuraxis; Neurons; Normal Range; Odds Ratio; Pain; Pain Measurement; Pain-Free; Pathology; Pathway interactions; Patients; Peripheral; Persistent pain; Phenotype; Population; Population Control; Process; Psychophysics; Relative (related person); Reporting; Research; Role; Secondary Hyperalgesias; Stimulus; Subgroup; Sum; Testing; Tissues; Variant; base; central pain; central sensitization; cohort; conditioning; experience; insight; patient population; pressure; prevent; public health relevance; response; sound; tibialis anterior muscle; tool

Project Summary/ Abstract Chronic musculoskeletal pain affects more Americans than diabetes, heart disease, and cancer combined according to the recent 2011 Institute of Medicine Pain Report. Pain is not simply a direct link between peripheral injury and the brain; both peripheral and central nervous system (CNS) modulation contribute to highly complex pain processing. Increasingly central sensitization of pain pathways is being recognized as an important component of persistent pain, but as central sensitization is a neuronal response, in humans it can only be indirectly assessed through psychophysical testing. Various evoked measures believed to be centrally-mediated; either through facilitated excitation (e.g., temporal summation of pain) or disinhibition (e.g., conditioned pain modulation, CPM) have been used to test for central mechanisms in a variety of musculoskeletal patient populations. Unfortunately, little has been done to characterize these central sensitivity assessments, thus it is unclear whether a single measure is equally representative of central involvement. While peripheral pain sensitivity phenotypes are modality-specific, e.g., individuals sensitive to heat pain are not necessarily sensitive to ischemic or cold pain, central sensitivity phenotypes have yet to be systematically examined. We are able to model central sensitization in humans using experimental muscle pain: referred pain and hyperalgesia at the ankle occurs in ~60% of individuals with intramuscular acidic infusion of the anterior tibialis. Thus we can use this model to test whether central sensitivity assessments are predictive of the development of referred pain. The first aim will characterize multiple central sensitivity phenotypes in humans: temporal summation of pain (i.e., punctate, deep-pressure and heat) and conditioned pain modulation (CPM, i.e., hypoalgesia to pressure and heat pain following noxious cold conditioning stimulus) and use cluster analyses to subgroup individuals based on their responses. The second aim will determine the likelihood that central sensitivity phenotypes are predictive of a model of central sensitization (i.e. referred pain). We will use logistic regression to determine the odd ratios of experiencing this reversible form of central sensitization between central sensitivity clusters. This study will either validate or challenge the common practice of using one or more of these assessments as equivalent markers of central sensitization in patient populations. When completed, these data can be used to direct and inform future studies as well as interpret previous findings in clinical populations. Long-term this information will be valuable for optimizing personalized therapies for patients with persistent pain conditions.

项目摘要/摘要 慢性肌肉骨骼疼痛比糖尿病、心脏病和癌症影响更多的美国人 根据最近的2011年医学研究所疼痛报告，综合起来。痛苦不仅仅是一种直接的联系 外周损伤与脑之间；外周和中枢神经系统(CNS)的调制 有助于高度复杂的疼痛处理。疼痛通路的中枢敏感化程度越来越高 被认为是持续性疼痛的重要组成部分，但作为中枢敏感化是一种 神经反应，在人类中，只能通过心理物理测试来间接评估。 各种被认为是集中调节的诱发措施；或者通过促进激发(例如， 疼痛的时间总和)或去抑制(例如，条件性疼痛调制，CPM 在各种肌肉骨骼疾病患者群体中测试中枢机制。不幸的是，几乎没有 已经完成了这些中央敏感性评估的特征，因此尚不清楚是否有单一的 MEASURE同样代表了中央参与。而外周疼痛敏感表型 是特定于形态的，例如，对热痛敏感的个人不一定对缺血或 冷痛、中枢敏感的表型还有待系统研究。我们有能力做模特 使用实验性肌肉痛的人类中枢敏感化：牵涉性疼痛和痛觉过敏 约60%的接受胫骨前肌酸性肌注入术的患者会出现踝关节。因此，我们 可以使用这个模型来测试中央敏感度评估是否可以预测 牵涉性疼痛。第一个目标将描述人类的多种中枢敏感性表型： 疼痛(即点状、深压和热)和条件性疼痛调制(CPM，即， 对伤害性冷条件刺激后的压力和热痛的痛觉减退)和使用CLUSE 根据个人的反应对其进行分组分析。第二个目标将决定 中枢敏感性表型预测中枢敏化模型的可能性(即 牵涉性疼痛)。我们将使用Logistic回归来确定经历这种可逆的奇数比 中央敏感团之间的中央敏化形式。这项研究将验证或 挑战将这些评估中的一个或多个用作 患者群体中的中枢敏感化。完成后，这些数据可用于指导和 为未来的研究提供信息，并解释先前在临床人群中的发现。从长远来看，这 信息将对优化持续性疼痛患者的个性化治疗非常有价值 条件。