Mechanisms of Action of Dorsal Root Ganglion Stimulation for Chronic Pain

背根神经节刺激治疗慢性疼痛的作用机制

基本信息

批准号：
10199761
负责人：
Robert Dwight Graham
金额：
$ 3.12万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2020-09-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10199761
关键词：
Affect Afferent Neurons Alternative Therapies American Analgesics Anatomic Models Anatomy Automobile Driving Biological Markers Cells Cessation of life Clinical Clinical Data Clinical Decision Support Systems Computer Models Data Disease Dorsal Electrodes Electromyography Electrophysiology (science)Ensure FDA approved Ganglia Goals Health Care Costs Histologic Histology Human Implant Individual Intractable Pain Knowledge Lead Location Magnetic Resonance Imaging Measurement Measures Medical Michigan Modeling Muscle Neurons Opioid Orthopedic Surgery Outcome Overdose Pain Pain Measurement Paint Paresthesia Patient-Focused Outcomes Patients Pharmaceutical Preparations Pharmacologic Substance Physiologic pulse Physiological Positioning Attribute Postoperative Period Prevalence Procedures Public Health Refractory Scanning Signal Transduction Societies Source Spinal Cord Spinal Ganglia Stimulus Subcellular Anatomy System Technology Testing Therapeutic United States Variant Visual Width X-Ray Computed Tomography analog base body map chronic pain clinical care clinical implementation clinical pain conventional therapy design experimental study first-in-human human data implementation outcomes improved insight interpatient variability neurophysiology new technology novel opioid epidemic pain inhibition pain relief predictive modeling relating to nervous system response therapy outcome treatment optimization

项目摘要

Project Summary The goal of this study is to elucidate the mechanisms of action of dorsal root ganglion stimulation (DRGS) for chronic pain. Chronic pain affects approximately 100 million Americans, and accounts for more than 600 billion dollars in healthcare costs each year. DRGS is an FDA-approved neurostimulation therapy for chronic pain that is refractory to conventional medical management. Although some patients receive sufficient pain relief in response to DRGS, clinical outcomes are often inconsistent. This variation in pain relief across patients may be due to poor understanding of the physiological mechanisms governing stimulation-induced pain relief. Therefore, we seek to uncover these mechanisms to ultimately optimize DRGS and improve clinical outcomes. This study is driven by previous computer modeling results from our lab showing that within stimulation parameter ranges used clinically, DRGS is likely driving the activity of large myelinated sensory neurons. In this proposed study, we will further investigate these mechanisms using computational models to determine sources of interpatient variability in DRGS outcomes. Furthermore, we will validate these models using clinical electrophysiological data, and inform the cellular anatomy of our models using histological data. We hypothesize that electrode location will be the largest source of variability in DRGS outcomes, and that positive DRGS outcomes will predict predominant activation of large myelinated sensory neurons. This project aims to characterize the mechanisms of action of DRGS to improve the implementation and outcomes of the therapy, and the models resulting from this project could be used to systematically design and test novel stimulation technologies (e.g. electrode and waveform design).

项目概要本研究的目的是阐明背根神经节刺激的作用机制 (DRGS) 用于慢性疼痛。慢性疼痛影响着大约 1 亿美国人，并导致更多每年的医疗费用超过 6000 亿美元。 DRGS 是 FDA 批准的一种神经刺激疗法传统医疗治疗难以治愈的慢性疼痛。尽管有些患者接受了足够的治疗 DRGS 的疼痛缓解效果，临床结果往往不一致。这种疼痛缓解的差异患者可能是由于对控制刺激引起的生理机制了解甚少缓解疼痛。因此，我们寻求揭示这些机制，以最终优化 DRGS 并改善临床结果。这项研究是由我们实验室之前的计算机建模结果驱动的，显示在根据临床使用的刺激参数范围，DRGS 可能驱动大有髓感觉的活动神经元。在这项拟议的研究中，我们将使用计算模型进一步研究这些机制确定 DRGS 结果中患者间变异的来源。此外，我们将验证这些模型使用临床电生理学数据，并使用组织学数据了解我们模型的细胞解剖学。我们假设电极位置将是 DRGS 结果变异的最大来源，并且阳性 DRGS 结果将预测大有髓感觉神经元的主要激活。本项目旨在描述 DRGS 的行动机制，以改善 DRGS 的实施和成果疗法，该项目产生的模型可用于系统地设计和测试新颖的刺激技术（例如电极和波形设计）。