Cortical Mapping of Neuropathic Low Back Pain

神经性腰痛的皮质映射

基本信息

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
项目类别：
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

项目摘要

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，无法治愈。约 30% 的 CLBP 患者患有神经性背痛，这被认为是由继发性神经根损伤引起的椎间盘退变和/或局部炎症。与不含神经病理成分的 CLBP 相比，神经病理成分 CLBP 与更多的患者痛苦（尤其是女性）、医疗并发症的严重程度增加相关医疗费用增加了 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的模型和临床研究迄今为止尚无有效的镇痛治疗方法。这个状态事件反映了我们对神经性 CLBP 病理生理学的有限理解以及对新药的需求镇痛治疗的目标。越来越多的证据表明大脑边缘系统和人类慢性疼痛病理生理学中的体感回路。我们的试点数据是最早的神经性 CLBP 中丘脑变小，丘脑和边缘系统功能连接发生改变与非神经性 CLBP 患者和健康对照相比。无论如何，系统地绘制这些神经性 CLBP 疼痛患者的神经回路仍然缺乏。该研究的目的是绘制结构和与非慢性 CLBP 相比，神经性 CLBP 的边缘系统和体感回路的功能特性神经性 CLBP 患者和匹配的健康对照。我们假设神经性 CLBP 患者会显示大脑体感系统的显着结构和功能改变。大脑结构和功能测量以及行为测量将分为 3 个研究组进行收集： (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 患者将根据经过验证的两步过程被分类为神经性或非神经性问卷（PainDETECT）和标准化疼痛评估工具，结合了感觉测试和针对神经性疼痛症状的经过验证的问题。所有参与者都将接受功能性脑成像收集静息状态的大脑活动和结构性大脑图像。皮质下脑体积、皮质厚度、将比较三组之间的白质连接性和功能连接性。在目标 1 中，我们将使用功能磁共振成像研究神经性 CLBP 与非神经性 CLBP 之间的大脑功能和结构差异和健康的匹配对照。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源自该提案的神经性 CLBP 的大脑生物标志物进行未来的验证研究位点，以及在人类和动物模型中开发新的治疗靶点。