Phenotyping Evoked Central Sensitivity to Painful Stimuli

描述(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超过糖尿病、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)的调制都有助于高度复杂的疼痛处理。疼痛通路的中枢敏感化越来越被认为是持续性疼痛的重要组成部分，但由于中枢敏感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。各种被认为是中枢调节的诱发措施，或者是通过促进兴奋(例如，疼痛的时间总和)，或者是通过去抑制(例如，条件性疼痛调制，CPM)，已经被用来在各种肌肉骨骼患者群体中测试中枢机制。不幸的是，几乎没有采取行动来确定这些中央敏感性评估的特征，因此，尚不清楚单一的衡量标准是否同样能代表中央参与。虽然外周疼痛敏感性表型是特定的，例如，对热痛敏感的个体不一定对缺血或冷痛敏感，但中枢敏感性表型尚未被系统地检测。我们能够使用实验性肌肉疼痛来模拟人类的中枢敏感化：大约60%的接受胫骨前部肌肉酸性输注的人会出现踝关节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性疼痛的发展。第一个目标将描述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)和条件性疼痛调制(CPM，即在有害的冷条件刺激后对压力和热痛的低痛觉)，并根据个体的反应使用聚类分析对其进行分组。第二个目标将确定中枢敏感性表型预测中枢敏感化模型(即牵涉性疼痛)的可能性。我们将使用Logistic回归来确定在中枢敏感簇之间经历这种可逆形式的中枢敏化的奇数比。这项研究将验证或挑战在患者群体中使用一种或多种评估作为中枢敏化的等效标志物的普遍做法。完成后，这些数据可用于指导和通知未来的研究，以及解释先前在临床人群中的发现。从长远来看，这些信息将对优化持续性疼痛患者的个性化治疗有价值。

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.