Cortical Pathophysiology of Pain

描述(由申请者提供)：目前对慢性背痛发展的了解是初步的。在上一次资助期间，我们的工作集中在发现脑源性生物标记物，这些标记物代表了临床慢性疼痛的状况。我们发现了一组特定的标记物，不仅可以区分慢性疼痛患者和健康受试者，还可以区分不同的慢性疼痛状况。在下一阶段的研究中，我们打算首次使用这些生物标记物来定义--第一次--伴随着亚急性疼痛向慢性疼痛过渡的大脑生理、解剖和代谢的时间变化，并将预测性标记物与慢性疼痛的后果区分开来。我们还将确定这些参数中的哪些参数在疼痛消退时逆转，从而确定慢性疼痛造成的脑损伤是暂时的还是永久性的。在目标1中，我们对亚急性背痛患者的脑形态、脑生理学和脑代谢标记物进行了18个月的纵向跟踪，因为他们正在过渡到慢性疼痛或疼痛缓解。脑生物标志物的变化是作为最终疼痛状态(慢性疼痛与消退)和从亚急性疼痛状态开始的时间的函数来研究的。根据我们在横断面研究中的结果，提出了关于这些标记物变化的假设。在目标2中，我们根据目标1的结果建立了一个预测模型，用于评估一个人从亚急性向慢性背痛转变的风险。在这个目标中，我们汇集了结果指标，并将它们一起用于预测向慢性疼痛的转变和向疼痛缓解的转变，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，以确定处于这种状态至少五年的慢性背痛患者的脑形态、脑生理和脑代谢标志物，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组进行比较，以确定哪些参数随着慢性疼痛持续数年而进展。我们之前的横断面研究表明，大脑在慢性背痛中起着突出的作用。在这里，我们测试了脑生物标记物在背痛从亚急性到慢性状态发展过程中的参与和致病作用。

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.