Mechanisms of Action of Dorsal Root Ganglion Stimulation for Chronic Pain

项目摘要 本研究的目的是阐明背根神经节刺激的作用机制 （DRGS）治疗慢性疼痛。慢性疼痛影响着大约1亿美国人，而且影响人数更多 超过6000亿美元的医疗费用。DRGS是FDA批准的神经刺激疗法，用于 传统医学治疗难以治愈的慢性疼痛。虽然有些病人接受了足够的 在响应于DRGS的疼痛缓解中，临床结果常常不一致。这种疼痛缓解的差异 患者可能是由于对控制刺激诱导的 缓解疼痛。因此，我们试图揭示这些机制，以最终优化DRGS并改善临床 结果。这项研究是由我们实验室以前的计算机建模结果驱动的，结果表明， 在临床上使用的刺激参数范围内，DRGS可能驱动大的有髓鞘感觉神经元的活动。 神经元在这项研究中，我们将进一步研究这些机制，使用计算模型， 确定DRGS结果中患者间变异性的来源。此外，我们将验证这些模型 使用临床电生理数据，并使用组织学数据告知我们模型的细胞解剖。 我们假设电极位置将是DRGS结果变异性的最大来源， 阳性DRGS结果将预测大的有髓鞘感觉神经元的主要激活。这个项目 旨在描述DRGS的行动机制，以改善 治疗，从这个项目产生的模型可以用来系统地设计和测试新的 刺激技术（例如电极和波形设计）。

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).