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与大脑之间的直接联系；周围神经系统和中枢神经系统（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中枢敏化被认为是持续性疼痛的重要组成部分，但由于中枢敏化是一种神经元反应，因此在人类中它只能通过心理物理测试来间接评估。各种诱发措施被认为是中央调节的；通过促进兴奋（例如，疼痛的时间总和）或去抑制（例如，条件性疼痛调节，CPM）已被用来测试各种肌肉骨骼患者群体的中枢机制。不幸的是，我们几乎没有采取任何措施来描述这些中央敏感性评估的特征，因此尚不清楚单一措施是否同样代表中央参与。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，但中枢敏感性表型尚未得到系统检查。我们能够使用实验性肌肉疼痛来模拟人类的中枢敏化：约 60% 的胫骨前肌肌内酸性输注患者会出现脚踝处的牵涉疼痛和痛觉过敏。因此我们可以使用这个模型 测试中枢敏感性评估是否可以预测牵涉疼痛的发展。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、深压和热）和条件性疼痛调节（CPM，即有害冷调理刺激后的压力和热痛痛觉减退）和使用根据个体的反应对亚组个体进行聚类分析。第二个目标将确定中枢敏感表型预测中枢敏感化模型（即牵涉痛）的可能性。我们将使用逻辑回归来确定中央敏感簇之间经历这种可逆形式的中央敏感化的奇数比。这项研究将验证或挑战使用这些评估中的一项或多项作为患者群体中枢敏化的等效标志物的常见做法。完成后，这些数据可用于指导和指导未来的研究，并解释以前在临床人群中的发现。从长远来看，这些信息对于优化持续性疼痛患者的个性化治疗非常有价值。