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

项目摘要 神经性疼痛可严重地使个体衰弱并降低个体生活质量，导致更多的临床症状。 访问和增加对阿片类药物的依赖性疼痛管理。背根神经节 已被证明是一种有效的治疗靶点，因为它的T-结过滤还可以替代 药理学在侵入性、局部性和有效性方面有很大的缺点。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， 神经性疼痛治疗范例。然而，应用聚焦超声治疗疼痛 治疗受到缺乏离体和体内研究工具的限制。在这份提案中，我将 开发新的离体和体内工具，研究聚焦超声在背根的应用 用于改善神经性疼痛病症的神经节。具体来说，我会设计一个新的协议， 解剖和记录经过DRG的中枢传入神经，并在 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， 确定背根神经节的FUS超声处理是否可以改善神经病理性疼痛 清醒行为小鼠的行为（目的2）。拟议的工作将产生新的体内和体外 聚焦超声治疗神经病理性疼痛的探索工具，促进临床 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.