Focused Ultrasound Neurostimulation of the Dorsal Root Ganglion for Neuropathic Pain Therapeutics

背根神经节聚焦超声神经刺激用于神经病理性疼痛治疗

• 批准号: 10493189
• 负责人: Stephen Alexander Lee
• 金额: $ 5.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10493189
• 关键词: Ablation; Address; Adjuvant Analgesic; Affect; Animals; Behavior; Brain; Clinical; Dependence; Development; Disease; Drug Delivery Systems; Effectiveness; Electric Stimulation; Electrophysiology (science); Engineering; Fentanyl; Focused Ultrasound; Focused Ultrasound Therapy; Frequencies; Goals; Gold; Immune response; In Vitro; Individual; Investigation; Ion Channel; Malignant Neoplasms; Measures; Mechanics; Mediating; Membrane; Methodology; Methods; Modality; Morphine; Mus; Nerve; Nerve Fibers; Nervous system structure; Neurons; Opiate Addiction; Opioid; Organ; Pain; Pain management; Pathway interactions; Peripheral; Peripheral Nerves; Pharmacology; Physiologic pulse; Placebos; Population; Positioning Attribute; Preparation; Protocols documentation; Quality of life; Research; Research Proposals; Signal Transduction; Skin; Sonication; Spinal Cord; Spinal Ganglia; Structure; Sufentanil; System; Technology; Therapeutic; Translating; Treatment Efficacy; Unipolar Neuron; Variant; Visit; Work; awake; base; behavior test; clinical translation; design; implantable device; improved; in vivo; mouse model; neuroregulation; non-opioid analgesic; novel; opioid misuse; opioid use; overtreatment; pain behavior; pain sensation; pain signal; painful neuropathy; pressure; relating to nervous system; response; standard care; therapeutic target; therapeutically effective; tool; ultrasound; voltage

Project Summary Neuropathic pain can severely debilitate and lower individual quality of life, leading to more clinical visits and an increased dependence on opioids for pain management. The dorsal root ganglion has been shown to be an effective therapeutic target due to its T-junction filtering yet alternatives to pharmacology have large drawbacks in invasiveness, locality, and effectiveness. Focused ultrasound is a unique noninvasive and spatially focused neuromodulation modality, poised to transform current neuropathic pain therapeutic paradigms. However, application of focused ultrasound for pain treatment is limited by the lack of tools for investigation ex vivo and in vivo. In this proposal, I will develop new ex vivo and in vivo tools to study the application of focused ultrasound to the dorsal root ganglion for improving neuropathic pain conditions. Specifically, I will engineer a new protocol for dissecting and recording central afferents past the DRG and measure T-junction filtering under optimal FUS sonication parameters (Aim 1). I will then establish an in vivo experimental setup to determine whether FUS sonication to the dorsal root ganglion can improve neuropathic pain behaviors in awake-behaving mice (Aim 2). The proposed work will generate novel in vivo and ex vivo tools for exploration of focused ultrasound treatment of neuropathic pain and facilitate clinical translation.

项目概要 神经性疼痛会严重削弱个人的生命质量，导致更多的临床症状。 就诊和对阿片类药物治疗疼痛的依赖增加。背根神经节有 由于其 T 形接头过滤作用以及替代品，已被证明是一种有效的治疗靶点 药理学在侵入性、局部性和有效性方面存在很大缺陷。聚焦超声 是一种独特的非侵入性和空间聚焦的神经调节方式，有望改变当前的 神经性疼痛治疗范例。然而，聚焦超声在疼痛方面的应用 由于缺乏离体和体内研究工具，治疗受到限制。在这个提案中，我将 开发新的离体和体内工具来研究聚焦超声在背根上的应用 神经节用于改善神经性疼痛状况。具体来说，我将为 解剖和记录经过 DRG 的中枢传入，并测量 T 结过滤 最佳 FUS 超声处理参数（目标 1）。然后我将建立一个体内实验装置 确定对背根神经节进行 FUS 超声处理是否可以改善神经性疼痛 清醒小鼠的行为（目标 2）。所提出的工作将产生新颖的体内和离体 探索聚焦超声治疗神经性疼痛并促进临床的工具 翻译。

项目成果

Interdependence of Tissue Temperature, Cavitation, and Displacement Imaging During Focused Ultrasound Nerve Sonication.

聚焦超声神经超声处理过程中组织温度、空化和位移成像的相互依赖性。

• 发表时间: 2023-07
• 作者: McCune, Erica P;Lee, Stephen A;Konofagou, Elisa E
• 通讯作者: Konofagou, Elisa E