Cortical Mapping of Neuropathic Low Back Pain

项目总结： 慢性腰背痛(CLBP)是一种无法治愈的致残性疾病。约30%的CLBP患者 患有神经病理性背痛，被认为是由于继发性神经根损伤引起的 退变的椎间盘和/或局部炎症。与不含神经性成分的CLBP相比， CLBP与更多的患者痛苦有关，特别是在女性中，增加了严重的医疗合并症 以及医疗保健成本增加了70%。尽管对周围神经损伤疼痛进行了广泛的临床前研究 神经性CLBP的模型及临床研究目前尚无有效的止痛治疗方法。这种状态 事件的发生反映了我们对神经性CLBP的病理生理学的有限的理解和对新事物的需要 止痛治疗的靶点。越来越多的证据表明，大脑边缘和大脑的 人体慢性疼痛病理生理学中的体感回路。我们的试点数据是首批 神经病理性CLBP患者丘脑缩小，丘脑和边缘系统功能连接改变 与非神经性CLBP患者和健康对照组比较。无论如何，系统地绘制这些地图 神经性CLBP疼痛患者的回路仍然缺乏。这项研究的目标是绘制出结构和 神经病理性CLBP与非CLBP边缘和躯体感觉回路的功能特性比较 神经病理性CLBP患者和匹配的健康对照组。我们假设神经性CLBP患者会 显示出大脑躯体感觉系统在结构和功能上的显著变化。 脑结构和功能测量以及行为测量将在3个研究组收集： (1)神经性CLBP患者(2)非神经性CLBP患者和(3)与健康对照组相匹配的参与者。 CLBP患者将在两个步骤的过程中被分类为神经性或非神经性，这一过程基于验证的 问卷(PainDETECT)和标准化的疼痛评估工具，该工具结合了感觉测试和 针对神经病理性疼痛症状的验证问题。所有参与者都将接受脑功能成像 收集静息状态的脑活动和结构脑图像。皮质下脑体积，皮质厚度， 将比较三组之间的白质连接和功能连接。在目标1中，我们将 用功能磁共振成像研究神经性CLBP与非神经病理性CLBP的脑功能和结构差异 和健康的配对对照组。在目标2中，我们将探索脑结构和功能的性别差异 神经病理性CLBP患者与非神经病理性CLBP患者和健康对照组比较。我们的长期目标是 使用从这一建议中得出的神经病理性CLBP的脑生物标记物进行未来的验证研究 用于在人类和动物模型中开发新的治疗靶点。

PROJECT SUMMARY: Chronic low-back pain (CLBP) is a disabling condition with no available cure. About 30% of CLBP patients suffer from neuropathic back pain, which is thought to arise from an injury to the nerve root secondary to degenerated discs and/or local inflammation. Compared to CLBP without a neuropathic component, neuropathic CLBP is associated with more patient distress, especially in women, increased severity of medical co-morbidities and a 70% increase in health care cost. Despite extensive pre-clinical studies of peripheral nerve injury pain models and clinical research on neuropathic CLBP there is no effective analgesic treatment to date. This state of affair reflects our limited understanding of the pathophysiology of neuropathic CLBP and the need for novel targets for analgesic treatment. Accumulating evidence point to a critical role of the brain limbic and somatosensory circuitries in the pathophysiology of chronic pain in humans. Our pilot data is among the first to show smaller thalamus and altered thalamic and limbic system functional connectivity in neuropathic CLBP compared to non-neuropathic CLBP patients and healthy controls. Regardless, systematic mapping of these circuitries in neuropathic CLBP pain patients is still lacking. The objective of the study is to map structural and functional properties of the limbic and somatosensory circuitries in neuropathic CLBP in comparison to non- neuropathic CLBP patients and matched healthy controls. We hypothesize that neuropathic CLBP patients will show significant structural and functional alterations in the brain somatosensory system. Brain structural and functional measures and behavioral measures will be collected in 3 study groups: (1) neuropathic CLBP patients (2) non-neuropathic CLBP patients and (3) matched healthy control participants. CLBP patients will be classified as neuropathic or non-neuropathic in a two-step process based on a validated questionnaire (PainDETECT) and a standardized evaluation of pain tool, which combines sensory testing and validated questions targeting neuropathic pain symptoms. All participants will undergo functional brain imaging to collect resting state brain activity and structural brain images. Sub-cortical brain volumes, cortical thickness, white matter connectivity and functional connectivity will be compared among the three groups. In Aim 1, we will use fMRI to study brain functional and structural differences between neuropathic CLBP, non-neuropathic CLBP and healthy matched controls. In Aim 2, we will explore sex differences in brain structure and function in neuropathic CLBP patients, compared to non-neuropathic CLBP and healthy controls. Our long-term goal is to use the brain biomarkers of neuropathic CLBP derived from this proposal for future validation studies across sites, and for developing novel therapeutic targets both in humans and in animal models.