Peripheral nerve stimulation for amputee pain

描述(申请人提供)：这项研究的长期目标是将一种治疗截肢后疼痛的神经刺激系统商业化。在美国，约有180万人接受截肢，每年约有18.5万人接受截肢。截肢后疼痛的发生率很高(95%)，并经常导致进一步的残疾、抑郁和生活质量下降。现有的长期止痛疗法长期效果不佳，而且价格昂贵(在美国，每年总计高达27亿至130亿美元)。我们成功地完成了之前的第一阶段项目，并在临床测试中展示了88%的受试者使用周围神经刺激(PNS)方法缓解截肢后疼痛的可行性，这种方法使用远离神经的单个电极选择性地激活目标纤维。此外，我们进行了一项为期2周的临时性经皮刺激的家庭试验，所有完成试验的受试者在接受24小时/天的刺激时，都经历了临床上显著的疼痛缓解(平均=76%)，证实只要提供刺激，疼痛缓解就可以持续。单个远端电极避免了以前限制三叉神经节的侵袭性。选择性远程刺激还允许使用灵活的自锚定导线，这将减少使用非弹性、非锚定导线的现有方法常见的并发症。此外，植入肢体的植入式脉冲发生器(IPG)将使铅能够在不越过臀部或肩部的情况下向肢体中的神经传递刺激。避免接缝减少了由于现有系统的硬件故障而频繁出现的重复弯曲/弯曲。目前第二阶段项目的目标是开发一种具有提供选择性远程刺激的技术能力的IPG，该刺激在先前的第一阶段研究中得到验证，可以缓解疼痛。需要新的IPG，因为没有现有的IPG可以提供选择性远程刺激所需的参数。此外，现有的IPG没有足够薄和轮廓足以舒适地放置在截肢者的残肢中，并能够提供提供高效止痛所需的独特刺激参数组合。为实现第二阶段目标，电池、包装和充电子系统将设计为能够植入四肢并安全充电(目标1)；电路板组件将设计为提供选择性远程刺激所需的刺激参数(目标2)；IPG将进行组装和安全可靠性测试(目标3)。如果每个目标的所有核查/确认测试都通过，则每个目标将被认为是成功的。这项工作的结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。在完成这项第二阶段研究后，IPG将 可用于未来获得FDA批准所需的临床前和临床研究。这种IPG的成功开发将完成商业刺激系统，该系统还包括一个试验系统和缠绕的、自锚定的可植入四肢PNS的导线理想。

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.