The Injectrode - A Truly Injectable Electrode for Dorsal Root Ganglion Stimulation to Treat Pain

摘要 考虑到“阿片类药物流行病”的压力以及成瘾药物可能对人体造成的巨大危害， 在患者中，对于治疗背痛的非阿片类替代品存在大量未满足的需求。背根神经节 (DRG)最近在临床研究中测试了刺激，与传统的硬膜外脊髓刺激进行了直接比较， 在一项152名患者的研究中，使用脊髓刺激（SCS）策略治疗顽固性疼痛。虽然受试者的百分比 在3个月时背痛减轻超过50%的患者在DRG中显著更高（81.2%） 组与SCS（55.7%）相比，与神经刺激器/器械或植入手术相关的不良事件发生率为 DRG组显著更高（分别为36.8%至26.4%和46.1%至26.3%）。作为程序， DRG和SCS涉及植入复杂的电极/导线/植入式脉冲发生器系统，两者的成本 程序也是一个重大障碍。 为了克服这些问题，我们开发了一种称为“注射电极”的新型电极， 注射器中的液体复合物，并在用杨氏注射器注射后迅速在神经鞘或神经孔中固化。 模量比现代DRG或SCS电极更接近人体组织。我们先前已经 展示了在深层神经上注射的能力，通过一根简单的电线连接到一个注射电极“收集器”， 注射到皮肤下，并使用标准的廉价非侵入性TENS可靠地刺激深层神经 没有任何跨越皮肤的电线连接。该系统只注入了简单的无源元件 为了创建从皮肤下到复杂神经结构（如孔/DRG）的传导管道， 显著减少了导致不良事件的故障点的数量。此外，作为刺激系统， 完全是外部的，它既更具成本效益，而且一旦新的刺激策略被采用， 发现可以减轻疼痛。在这项研究中，我们建议直接比较注射电极/注射电极收集器 这是一个概念，以建立电极刺激策略的DRG作为替代阿片类药物管理。 我们将进行必要的实验室表征和改进，作为FDA启用的临床试验的先驱。 研究，在适当大小的动物模型中使用建模和动物试验来改进能量的效率 从TENS装置转移到注射电极/注射电极收集器概念，并优化注射手术 背根神经节复杂解剖结构的手术。

Abstract Given the pressures from the ‘opioid epidemic’ and the substantial harm the addictive drugs may have on patients, there is a substantial unmet need for non-opioid alternatives to treat back pain. Dorsal Root Ganglion (DRG) stimulation has recently been tested in clinical studies in direct comparison to traditional epidural spinal cord stimulation (SCS) strategies for intractable pain in a 152 patient study. Although the percentage of subjects received greater than 50 percent decrease in back pain at 3 months was significantly greater in the DRG (81.2%) arm vs SCS (55.7%), the adverse event rate related to the neural stimulator/device or the implant procedure was significantly higher in the DRG arm (36.8% to 26.4% and 46.1% to 26.3%, respectively). As the procedure for DRG and SCS involve implanting a complex electrode/lead/implantable pulse generator system, the cost of both procedures is also a significant barrier. To overcome these issues, we have developed a novel electrode called the ‘Injectrode’, which is pre-polymer liquid composite in a syringe and cures in a neural sheathe or foramen quickly after injection with a Young’s Modulus substantially closer to human tissue than contemporary DRG or SCS electrodes. We have previously demonstrated the ability to inject on a deep nerve, connect via a simple wire to an Injectrode ‘collector’ that is injected under the skin, and reliably stimulate the deep nerve using a standard inexpensive non-invasive TENS unit without any wire connection spanning the skin. This system has only simple passive components injected to create a conductive conduit from just under the skin to complex neural structures like the foramen/DRG, dramatically reducing the number of failure points leading to adverse events. Moreover, as the stimulating system is entirely external, it is both much more cost efficient and easily upgradable once new stimulation strategies are discovered to reduce pain. In this study, we propose to directly compare the Injectrode/Injectrode collector concept to established electrode stimulation strategies for the DRG as an alternative to opioid administration. We will perform benchtop characterization and refinement necessary as a precursor to an FDA enabled clinical study, use modeling and animal testing in appropriate sized animal models to refine the efficiency of energy transfer from a TENS unit to an Injectrode/Injectrode collector concept, and optimize the injection surgical procedure for the complex anatomy of the DRG.