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

项目摘要 神经性疼痛可严重削弱个人生活质量并降低个人生活质量，导致更多的临床 就诊和疼痛控制方面对阿片类药物的依赖增加。背根神经节有 已被证明是一种有效的治疗靶点，因为它的T形连接过滤，但替代 药理学在侵入性、地方性和有效性方面有很大的缺陷。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，有望改变电流 神经病理性疼痛治疗范例。然而，聚焦超声在疼痛治疗中的应用 由于缺乏体内外研究工具，治疗受到限制。在这份提案中，我将 开发新的体内外工具研究聚焦超声在背根中的应用 神经节，用于改善神经病理性疼痛状况。具体地说，我将设计一个新的协议，用于 解剖和记录通过背根神经节的中央传入和测量T形交界处的滤波 最佳超声参数(目标1)。然后我将建立一个体内实验装置来 确定超声刺激背根神经节是否能改善神经病理性疼痛 清醒行为小鼠的行为(目标2)。拟议的工作将在体内和体外产生新的 探索聚焦超声治疗神经病理性疼痛的工具，方便临床 翻译。

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.