Cortical Mapping of Neuropathic Low Back Pain

神经性腰痛的皮质映射

• 批准号: 10040696
• 负责人: Paul Geha
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10040696
• 关键词: Acute; Affect; Analgesics; Animal Model; Anxiety; Area; Back Pain; Biological Markers; Brain; Brain imaging; Chronic; Chronic low back pain; Clinical Research; Data; Development; Direct Costs; Disease; Distress; Evaluation; Facilities and Administrative Costs; Female; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Health Care Costs; Healthcare; Human; Hyperalgesia; Individual; Inflammation; Injury; Limbic System; Low Back Pain; Lower Extremity; Maps; Measures; Medical; Mental Depression; Motor; Nerve; Neuropathy; Opioid Analgesics; Pain; Participant; Patients; Peripheral nerve injury; Pharmaceutical Preparations; Pharmacology; Placebos; Plant Roots; Primary Health Care; Process; Property; Publishing; Questionnaires; Radiating Pains; Radiculopathy; Rest; Risk; Role; Sciatica; Secondary to; Sensory; Severities; Sex Differences; Site; Societies; Spinal Diseases; Standardization; Structure; Subgroup; Symptoms; System; Testing; Thalamic structure; Therapeutic; Thick; Translational Research; Vertebral column; Woman; base; behavior measurement; brain volume; chronic pain; chronic pain patient; comorbidity; cortex mapping; disability; economic cost; foot; male; new therapeutic target; novel; pain model; pain patient; pain symptom; painful neuropathy; preclinical study; prescription opioid; relating to nervous system; somatosensory; substance misuse; tool; validation studies; virtual; white matter

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.

项目概要： 慢性腰痛（CLBP）是一种致残性疾病，目前尚无有效的治疗方法。大约30%的CLBP患者 患有神经性背痛，这被认为是由继发于神经根损伤引起的， 椎间盘退变和/或局部炎症。与不含神经性组分的CLBP相比，神经性 CLBP与更多的患者痛苦相关，尤其是女性患者，增加了医疗合并症的严重程度 医疗费用增加了70%。尽管对周围神经损伤疼痛的临床前研究 神经病理性CLBP的模型和临床研究，迄今为止还没有有效的镇痛治疗。该状态 事件的发生反映了我们对神经性CLBP的病理生理学的有限理解，以及对新的治疗方法的需要。 镇痛治疗的靶点。越来越多的证据表明，大脑边缘系统和 人体慢性疼痛病理生理学中的躯体感觉回路。我们的试点数据是第一批 显示神经性CLBP中丘脑变小，丘脑和边缘系统功能连接改变 与非神经性CLBP患者和健康对照组相比。无论如何，系统地绘制这些 神经性CLBP疼痛患者的电路仍然缺乏。这项研究的目的是绘制结构图， 神经性CLBP与非神经性CLBP相比， 神经性CLBP患者和匹配的健康对照。我们假设神经性CLBP患者 显示出大脑躯体感觉系统的结构和功能发生了重大变化。 将在3个研究组中收集大脑结构和功能测量以及行为测量： (1)神经性CLBP患者，（2）非神经性CLBP患者和（3）匹配的健康对照参与者。 CLBP患者将基于经验证的神经病理学指标在两步过程中被分类为神经性或非神经性。 问卷（PainDETECT）和疼痛工具的标准化评估，该工具结合了感觉测试和 针对神经性疼痛症状的验证问题。所有参与者将接受功能性脑成像 收集静息状态下的大脑活动和大脑结构图像。皮层下脑容量皮层厚度， 将在三组之间比较白色物质连接和功能连接。在目标1中，我们 使用fMRI研究神经性CLBP、非神经性CLBP之间的脑功能和结构差异， 健康对照组。在目标2中，我们将探讨大脑结构和功能的性别差异， 神经性CLBP患者与非神经性CLBP和健康对照相比。我们的长期目标是 使用来自该提议的神经性CLBP的脑生物标志物进行未来的验证研究， 位点，并用于在人类和动物模型中开发新的治疗靶点。