Development of A Focused Ultrasound Device for Noninvasive, Peripheral Nerve Blockade to Manage Acute Pain

开发用于非侵入性周围神经阻断来治疗急性疼痛的聚焦超声装置

• 批准号: 10740796
• 负责人: Thomas A. Anderson
• 金额: $ 250.55万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2026-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740796
• 关键词: Acoustics; Action Potentials; Acute Pain; Acute pain management; Adult; Adverse effects; Analgesics; Animal Model; Area; Back; Behavioral; Capsaicin; Caring; Clinical; Clinical Trials; Cutaneous; Development; Devices; Dimethyl Sulfoxide; Dose; Fiber; Focused Ultrasound; Frequencies; Geometry; Goals; Health Care Costs; Histologic; Human; Industry; Injections; Investigation; Knowledge; Laboratories; Lateral; Length; Local Anesthetics; Macaca fascicularis; Mediating; Medical Device; Modeling; Motor; Myocardial Ischemia; Nerve; Nerve Block; Nerve Fibers; Nociception; Nociceptors; Opioid; Pain; Pain management; Patients; Peripheral Nerves; Quality of life; Rattus; Research Personnel; Risk; Risk Reduction; Rodent; Rodent Model; Structure; Surgical incisions; Techniques; Technology; Testing; Time; Translating; Translations; Ultrasonic Transducer; Width; addiction; adverse outcome; allodynia; chronic pain; comparison control; design; effective therapy; experimental study; foot; health care settings; improved; in vivo; lens; nonhuman primate; novel; opioid epidemic; pain model; pain outcome; painful neuropathy; prescription opioid; pressure; prevent; prototype; scale up; sciatic nerve; side effect; technology development; technology/technique; tool; ultrasound

Abstract The US opioid epidemic developed in large part as a result of the widespread prescription of opioids for the treatment of acute pain. Moderate and severe acute pain are prevalent in many healthcare settings and associated with adverse outcomes (e.g., increased risk of myocardial ischemia, worsened quality of life, increased healthcare costs). Current acute pain management strategies (systemic analgesics and peripheral nerve blocks (PNBs)) insufficiently treat pain. Systemic analgesics, e.g., opioids, are inadequate for controlling acute pain (as they primarily block C nociceptive fibers, not A-delta nociceptive fibers) and have many harmful side effects, frequently resulting in addiction. Current PNB techniques, via the injection of local anesthetics at peripheral nerves, improve acute pain outcomes for some patients but have significant shortcomings limiting use (e.g, they are invasive, increase care complexity, and only manage acute pain for a limited amount of time). FUS-induced PNB is a ground- breaking technology/technique that may serve as an alternative to traditional local anesthetic-based PNB, preventing the need for opioids to manage acute pain, and reducing the risk of developing chronic pain. This proposal outlines aims to translate FUS technology into a novel medical device for noninvasive PNB to improve acute pain management leading to a dramatic paradigm shift in acute pain treatment. Prior investigations support FUS’s potential for managing acute pain. Investigators have found that application of FUS to peripheral nerves in ex vivo and in vivo animal models results in dose- dependent reversible reduction in peripheral nerve compound action potential amplitude and a transient increase in nociceptive thresholds in rodent neuropathic pain models with reversible effects on nerve structure. In an in vivo rodent model of acute pain, we determined FUS parameters for reversible blockade of peripheral nerve fibers. Further, we have demonstrated that FUS can be applied transcutaneously to block peripheral nerve function. FUS-induced PNB as a novel clinical tool for managing acute pain is held back by several addressable gaps in knowledge and need for technological development: 1) An insufficient understanding of the optimal parameters for transcutaneous (noninvasive) FUS application to peripheral nerves resulting in reversible blockade and without adverse effects; 2) No available FUS device with the frequency and focal zone (high pressure area) geometry required for application to non-human primate (NHP) and human peripheral nerves; and 3) Absence of studies evaluating transcutaneous FUS application to peripheral nerves for reversible PNB in a NHP model of acute pain. The present Aims will address the existing barriers preventing clinical trials investigating FUS-induced PNB for acute pain management.

抽象的 美国阿片类流行很大程度上是由于阿片类药物的宽度处方而发展 急性疼痛的治疗。在许多医疗机构中，中度和严重的急性疼痛普遍存在 并与不良结果相关（例如，心肌缺血的风险增加，质量恶化 生活，增加医疗费用）。当前的急性疼痛管理策略（全身镇痛药 和周围神经障碍物（PNB））治疗疼痛。全身性镇痛药，例如阿片类药物是 无法控制急性疼痛（当它们主要阻断伤害感受纤维，而不是A-delta） 伤害性纤维）并具有许多有害的副作用，经常导致成瘾。当前的PNB 通过在周围神经系统中注入局部麻醉药，技术改善了急性疼痛结果 一些患者，但存在明显的缺点（例如，它们具有侵入性，增加护理 复杂性，仅在有限的时间内治疗急性疼痛）。 FUS诱导的PNB是接地 破坏技术/技术，可以替代传统的基于局部麻醉的局部麻醉 PNB，阻止阿片类药物管理急性疼痛，并降低患慢性的风险 疼痛。该提案概述旨在将FUS技术转化为一种新颖的医疗设备 无创PNB改善急性疼痛管理，导致急性疼痛的巨大范式转移 治疗。先前的投资支持FUS管理急性疼痛的潜力。调查人员有 发现在离体和体内动物模型中，FUS在外周神经中的应用导致剂量 - 外周神经复合动作电势放大器的依赖性可逆降低和瞬态 啮齿动物神经性疼痛模型中的伤害性阈值增加，对神经具有可逆作用 结构。在急性疼痛的体内啮齿动物模型中，我们确定了可逆的FUS参数 周围神经纤维的封锁。此外，我们已经证明了可以应用FUS 经智慧地阻断周围神经功能。 FUS诱导的PNB是一种新型的临床工具 管理急性疼痛受到知识和需求的几个可寻址差距的阻碍 技术发展：1）对最佳参数的理解不足 经皮（非侵入性）FUS应用于周围神经的施用会导致可逆的封锁和 没有不利影响； 2）没有带有频率和焦距的FUS设备（高压 区域）将其应用于非人类灵长类动物（NHP）和人类外周神经所需的几何形状； 3）缺乏评估经皮菌FUS应用于外周神经的研究 NHP急性疼痛模型中的可逆PNB。目前的目标将解决现有的障碍 防止研究FUS诱导的PNB进行急性疼痛管理的临床试验。