Phenotyping Evoked Central Sensitivity to Painful Stimuli

描述（由申请人提供）：根据最近的2011年医学疼痛研究所报告，慢性肌肉骨骼疼痛对美国人的影响超过了糖尿病，心脏病和癌症的总和。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）的调节都参与高度复杂的疼痛处理。越来越多的疼痛通路的中枢敏化被认为是持续疼痛的重要组成部分，但由于中枢敏化是一种神经元反应，在人类中只能通过心理物理测试间接评估。各种诱发措施被认为是中央介导的；通过促进兴奋（例如，疼痛的时间累积）或解除抑制（例如，条件疼痛调节，CPM）已被用于测试各种肌肉骨骼患者群体的中枢机制。不幸的是，对这些中心敏感性评估的特征所做的工作很少，因此尚不清楚单一措施是否能同样代表中心参与。虽然外周疼痛敏感性表型是模式特异性的，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的研究。我们能够通过实验肌肉疼痛来模拟人类的中枢致敏：60%的人在胫骨前肌内注射酸液后会出现踝关节的牵涉性疼痛和痛觉过敏。因此我们可以使用这个模型

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.