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: 8813536
• 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/8813536
• 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; Health; 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; peripheral pain; personalized medicine; pressure; prevent; response; sound; tibialis anterior muscle; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：根据最近的2011年医学研究所疼痛报告，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。疼痛不仅仅是外周损伤与大脑之间的直接联系。外围和中枢神经系统（CNS）调节都有助于高度复杂的疼痛处理。疼痛途径的越来越多的中心敏化被认为是持续疼痛的重要组成部分，但是由于中心敏化是一种神经元反应，在人类中，只能通过心理物理测试来间接评估。据信被认为是集中介导的各种诱发措施；通过促进的激发（例如，疼痛的时间求和）或抑制作用（例如条件疼痛调节，CPM）已用于测试各种肌肉骨骼患者人群中的中心机制。不幸的是，几乎没有完成这些中心灵敏度评估的表征，因此尚不清楚单个措施是否同样代表中心参与。虽然外周疼痛敏感性表型是特异性特异性的，但是，对热疼痛敏感的个体不一定对缺血性或冷疼痛敏感，但中枢灵敏度表型尚未系统地检查。我们能够使用实验性肌肉疼痛对人类的中心敏化进行建模：踝关节的引用疼痛和痛觉过敏发生在约60％的肌肉内酸性注入前胫骨前的个体中。因此我们可以使用此模型 测试中央灵敏度评估是否可以预测转介疼痛的发展。第一个目的将表征人类中多种中心敏感性表型：疼痛的时间求和（即点状，深压和热量）和条件疼痛调节（即CPM，即在有害冷条件刺激下对压力和热疼痛的降压和热疼痛），并根据其反应来对子组进行分析。第二个目的将决定中央灵敏度表型可以预测中心敏化模型（即引用疼痛）的可能性。我们将使用逻辑回归来确定中央灵敏度簇之间体验这种可逆形式的中心敏化形式的奇数比率。这项研究将验证或挑战使用其中一种或多种评估作为患者人群中心敏化的等效标志的共同做法。完成后，这些数据可用于指导和告知未来的研究，并解释临床人群中先前的发现。长期此信息对于针对持续性疼痛状况的患者优化个性化疗法将是有价值的。