Peripheral nerve stimulation for amputee pain

描述（由申请人提供）：本研究的长期目标是将神经刺激系统商业化，以治疗截肢后疼痛。在美国，大约有180万人接受截肢手术，每年大约有185，000人接受截肢手术。截肢后疼痛的发生率很高（95%），经常导致进一步的残疾，抑郁和生活质量下降。现有的长期疼痛治疗是不充分的长期和昂贵的（总计高达2.7 - 13亿美元/年在美国）。 我们成功完成了之前的I期项目，并证明了在临床试验期间使用外周神经刺激（PNS）方法缓解88%受试者截肢后疼痛的可行性，该方法使用远离神经放置的单个电极选择性激活目标纤维。此外，我们进行了一项为期2周的临时经皮刺激家庭试验，所有完成试验的受试者在接受24小时/天刺激时均经历了临床显著的疼痛缓解（平均= 76%），证实只要提供刺激，疼痛缓解就可以持续。单个远程电极避免了以前限制PNS的侵入性。选择性远程刺激还使得能够使用柔性的自锚定引线，这将减少使用无弹性的非锚定引线的现有方法常见的并发症。同样，设计用于放置在肢体中的植入式脉冲发生器（IPG）将使电极导线能够在不穿过髋关节或肩部的情况下向肢体中的神经输送刺激。避免接头可以减少因现有系统硬件故障而经常发生的重复弯曲/弯折。本II期项目的目标是开发一种IPG，其技术能力可提供经验证的选择性远程刺激，以缓解先前I期研究中的疼痛。需要新的IPG，因为现有IPG无法提供选择性远程刺激所需的参数。此外，没有现有的IPG足够薄且轮廓足够大以舒适地放置在截肢者的残肢中并且能够递送提供高效疼痛缓解所需的刺激参数的独特组合。 为实现第II阶段目标，电池、包装和充电子系统的设计将能够植入肢体并安全充电（目标1）;电路板组件的设计将能够提供选择性远程刺激所需的刺激参数（目标2）; IPG的组装和安全性和可靠性测试（目标3）。如果通过了相应目标的所有验证/确认测试，则每个目标将被视为成功。这项工作的成果将是一个可充电的IPG，可以提供选择性的远程刺激，这被证明是非常有效的截肢后疼痛。完成本II期研究后，IPG将 准备用于获得FDA批准所需的未来临床前和临床研究。该IPG的成功开发将完善商业刺激系统，该系统还包括试验系统和盘绕的自锚式植入式电极导线，非常适用于四肢中的PNS。

DESCRIPTION (provided by applicant): The long term goal of this research is to commercialize a neurostimulation system to treat post- amputation pain. Approximately 1.8 million individuals in the U.S. are living with an amputation, and about 185,000 individuals undergo an amputation each year. Post-amputation pain has a high incidence (95%) and frequently causes further disability, depression, and reductions in quality of life. Existing long-term pain therapies are inadequate long-term and are expensive (totaling up to $2.7-13 Billion/yr in the U.S.). We successfully completed the previous Phase I project and demonstrated the feasibility of relieving post- amputation pain in 88% of subjects during in-clinic testing with a method of peripheral nerve stimulation (PNS) that selectively activates target fibers using a single electrode placed remote from the nerve. Also, we conducted a 2-wk home trial of temporary percutaneous stimulation, and all subjects that completed the trial experienced clinically significant pain relief (average=76%) while receiving 24hr/day stimulation, confirming that pain relief can be sustained as long as stimulation is delivered. Single remote electrodes avoid the invasiveness previously limiting PNS. Selective remote stimulation also enables the use of a flexible, self- anchoring lead, which will reduce complications common with existing methods that use inelastic, non- anchoring leads. As well, implantable pulse generators (IPG) designed to be placed in the limb would enable the lead to deliver stimulation to nerves in the limbs without crossing the hip or shoulder. Avoiding joints reduces the repeated flexing/bending that frequently because hardware failures with existing systems. The goal of the present Phase II project is to develop an IPG with the technical capability to deliver the selective remote stimulation validated to relieve pain in the previous Phase I study. The new IPG is needed because no existing IPG can deliver the required parameters for selective remote stimulation. Also, no existing IPG is sufficiently thin and contoured to be placed comfortably in the amputee's residual limb and able to deliver the unique combination of stimulation parameters necessary to provide highly effective pain relief. To achieve the Phase II goal, the battery, packaging, and charging subsystem will be designed to enable implantation in the limbs and safe recharging (Aim 1); the circuit board assembly will be designed to deliver the required stimulation parameters for selective remote stimulation (Aim 2); and the IPG be assembled and tested for safety and reliability (Aim 3). Each aim will be considered successful if all verification/validation tests for the respective aims are passed. The outcome of this work will be a rechargeable IPG that can deliver selective remote stimulation, which was demonstrated to be highly effective for post-amputation pain. After completion of this Phase II study, the IPG will be ready for use in future preclinical and clinical studies required to obtain FDA approval. The successful development of this IPG will complete the commercial stimulation system, which also consists of a trial system and coiled, self-anchoring implantable lead ideal for PNS in the limbs.