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，慢性肌肉骨骼疼痛影响的美国人比糖尿病，心脏病和癌症的总和还要多。疼痛不仅仅是外周损伤和大脑之间的直接联系;外周和中枢神经系统（CNS）调节都有助于高度复杂的疼痛处理。越来越多的疼痛通路的中枢致敏被认为是持续性疼痛的重要组成部分，但由于中枢致敏是一种神经元反应，在人类中只能通过心理物理测试间接评估。各种被认为是中枢介导的诱发测量;或者通过易化兴奋（例如，疼痛的时间总和）或去抑制（例如，条件性疼痛调节，CPM）已被用于测试各种肌肉骨骼患者群体中的中枢机制。不幸的是，几乎没有做这些中央敏感性评估的特点，因此，目前还不清楚是否有一个单一的措施是同样代表中央参与。虽然外周疼痛敏感性表型是模态特异性的，例如，对热痛敏感的个体不一定对缺血性或冷痛敏感，中枢敏感性表型还有待系统地检查。我们能够使用实验性肌肉疼痛来模拟人类的中枢致敏：踝关节的牵涉痛和痛觉过敏发生在约60%的胫骨前肌肌内酸输注的个体中。因此，我们可以使用这个模型 以测试中枢敏感性评估是否可预测牵涉性疼痛的发展。第一个目标将表征人类的多种中枢敏感性表型：疼痛的时间总和（即，点状、深压和加热）和条件性疼痛调节（CPM，即，对有害的冷条件刺激后的压力和热疼痛的痛觉减退），并基于其反应对亚组个体使用聚类分析。第二个目的是确定中枢敏感性表型预测中枢致敏（即牵涉痛）模型的可能性。我们将使用逻辑回归来确定中枢敏感性集群之间经历这种可逆形式的中枢敏感化的比值比。本研究将验证或挑战使用一项或多项这些评估作为患者人群中中枢致敏的等效标志物的常见做法。完成后，这些数据可用于指导和通知未来的研究，以及解释临床人群中以前的发现。长期而言，这些信息对于优化持续性疼痛患者的个性化治疗具有重要价值。