Cortical Pathophysiology of Pain

描述（由申请人提供）：目前对慢性背痛发展的理解是初步的。在上一个资助期间，我们的工作重点是发现代表临床慢性疼痛状况的脑源性生物标志物。我们发现了一组特定的标志物，不仅可以区分慢性疼痛患者和健康受试者，还可以区分各种慢性疼痛状况。在下一阶段的研究中，我们打算使用这些生物标志物来定义-第一次-伴随从亚急性到慢性疼痛过渡的大脑生理学，解剖学和代谢的时间变化，并将预测标记物与慢性疼痛的结果区分开来。我们还将确定当疼痛消退时，这些参数中的哪些会逆转，从而确定慢性疼痛引起的脑损伤是暂时的还是永久的。在目标1中，我们纵向跟踪亚急性背痛患者的脑形态学、脑生理学和脑代谢标志物，持续18个月，因为他们过渡到慢性疼痛或疼痛消退。研究脑生物标志物的变化作为最终疼痛状态（慢性与缓解）和从亚急性疼痛状态开始的时间的函数。假设是先进的关于这些标志物的变化的基础上，我们在横断面研究的结果。在目标2中，我们根据目标1的结果建立了一个预测模型，用于评估从亚急性背痛过渡到慢性背痛的风险。在这个目标中，我们汇集的结果的措施，并使用它们一起预测过渡到慢性疼痛和疼痛的决议，以及预测亚急性和慢性疼痛的临床特征。在目标3中，我们进行了一项横断面病例对照研究，以确定慢性背痛患者的脑形态学，脑生理学和脑代谢标志物，这些患者至少已患病5年，并将这些参数与目标1中研究的亚急性人群和匹配的健康对照受试者进行对比，以确定哪些参数随着慢性疼痛持续数年而进展。我们以前的横断面研究表明，大脑在慢性背痛中起着重要作用。在这里，我们测试的参与和因果关系的作用，脑生物标志物的进展，背痛从亚急性到慢性状态。

DESCRIPTION (provided by applicant): Current understanding of the development of chronic back pain is rudimentary. In the last funding period our work focused on discovering brain-derived biomarkers typifying clinical chronic pain conditions. We uncovered a specific set of markers that not only distinguish chronic pain patients from healthy subjects, but also differentiate among various chronic pain conditions. In this next phase of study we intend to use these biomarkers to define - for the first time - temporal changes in brain physiology, anatomy, and metabolism that accompany the transition from sub-acute to chronic pain, and to distinguish predictive markers from those that are a consequence of the chronic pain. We will also identify which of these parameters reverse when the pain subsides, thereby determining if brain injury caused by chronic pain will be transient or permanent. In Aim 1, we longitudinally track brain morphology, brain physiology, and brain metabolic markers in subacute back pain patients for 18 months as they transition to either chronic pain or pain resolution. Changes in brain biomarkers are studied as a function of the final pain state (chronic vs. resolution) and of the time from subacute pain state. Hypotheses are advanced regarding changes in these markers based on our results in cross-sectional studies. In Aim 2, we build a predictive model for assessing one's risk for transitioning from subacute to chronic back pain based on the results of Aim 1. In this aim we pool the outcome measures and use them together for predicting transitions to chronic pain and to pain resolution, as well as for predicting the clinical characteristics of subacute and chronic pain. In Aim 3, we perform a cross-sectional case-control study to determine brain morphology, brain physiology, and brain metabolic markers in chronic back pain patients who have been in the condition for at least five years, and contrast these parameters to both the subacute population studied in Aim 1 and to matched healthy control subjects, in order to determine which parameters progress as chronic pain is sustained for several years. Our previous cross-sectional studies show that the brain plays a prominent role in chronic back pain. Here we test the involvement and causative role of brain biomarkers in the progression of back pain from a subacute to a chronic state.