Phenotyping Evoked Central Sensitivity to Painful Stimuli

项目总结/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。疼痛不仅仅是 外周损伤和大脑之间;外周和中枢神经系统（CNS）调节 有助于高度复杂的疼痛处理。疼痛通路的中枢敏感性越来越高， 被认为是持续性疼痛的重要组成部分，但作为中枢敏化， 在人类中，它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，条件性疼痛调制（CPM） 以测试各种肌肉骨骼患者人群的中枢机制。不幸的是， 已经完成了对这些中心敏感性评估的描述，因此尚不清楚是否有一个单一的 这一措施同样代表了中央参与。而外周疼痛敏感性表型 是模态特定的，例如，对热痛敏感的个体不一定对缺血性或 冷痛、中枢敏感性表型还有待系统地研究。我们能够模拟 利用实验性肌肉疼痛对人类中枢致敏作用的研究： 踝关节发生在约60%的胫骨前肌肌内酸灌注的个体中。因此我们 可以使用该模型来测试中枢敏感性评估是否可以预测 涉及疼痛。第一个目标将描述人类的多种中枢敏感性表型：颞叶神经元和颞叶神经元。 疼痛的总和（即，点状、深压和加热）和条件性疼痛调节（CPM，即， 在有害冷条件刺激后对压力和热疼痛的痛觉减退）和使用群集 根据亚组个体的反应进行分析。第二个目标将决定 中枢敏感性表型预测中枢致敏模型的可能性（即， 疼痛）。我们将使用逻辑回归来确定经历这种可逆性的几率。 中枢敏感性簇之间的中枢敏感化形式。本研究将验证或 挑战使用一项或多项评估作为 患者人群的中枢致敏作用。完成后，这些数据可用于指导和 为未来的研究提供信息，并解释临床人群中以前的发现。长期这个 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 条件

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.