Novel Implantable Device to Negate Post-Amputation Pain

7.项目总结/摘要 据估计，到2050年，将有大约360万美国人失去肢体，也就是说， 截肢不幸的是，大多数患者会经历慢性截肢后疼痛 （CPAP），已发现高达80%的患者在截肢后长达20年内发生。 CPAP可以在缺失肢体的残端感觉到（残肢疼痛或残端疼痛），也可以感觉到 失去的肢体仍然存在（幻肢痛）。到目前为止，还没有一致推荐的治疗方法。 对于这种疼痛，可用的治疗（包括阿片类药物和其他药物）通常 不足以实现良好的疼痛控制。 一些研究已经观察到，将麻醉剂直接递送到神经损伤中的损伤神经， 截肢残端可以阻止CPAP的发作，甚至在某些患者中有效抑制CPAP。这 可能是一种有前途的治疗方法，但患者难以管理：它涉及放置导管 通过皮肤进入神经鞘，麻醉药物在流体中通过鞘持续流动， 由输液泵驱动，输液泵必须不断地进行输液。一种更好的麻醉剂输送方法 从长远来看，直接对受伤的神经进行治疗并不那么麻烦，这将是一个重大进步。 我们现在建议开发一种能够完成这项任务的设备：Novelix PainGuard （NPG）。NPG构建体源自FDA批准的透析技术;它们由网状结构组成。 含有微孔的纤维。网状物/纤维可以以非常高的浓度负载麻醉药物。 然后慢慢地渗入到周围的环境中。NPG设备可以通过手术放置在 在截肢时损伤神经，使得NPG内的麻醉剂使神经麻木 当它离开PainGuard装置时，它会持续地移动。此外，NPG装置可以附接到填充端口， 也放置在皮肤下;该端口可用于在办公室访问中通过简单的注射重新填充NPG （类似于疫苗注射，但直接进入皮肤下的端口）。这可以允许NPG运行， 非常长的时间段，数月或甚至数年，甚至可能是一生。 在这个提案中，我们的目标是设计NPG设备，对疼痛控制有最大的效果， 最长的一段时间，而不需要重新填充。我们将改变和测试NPG的不同设计功能， 包括微孔的尺寸和密度，使用“润湿剂”以促进（或延伸） 我们将在大鼠神经损伤模型中测试最有前途的NPG设计 并证明我们一次充电就能缓解至少一个月的疼痛。然后我们将 建立一个更大版本的NPG与灌装端口连接，并在兔子中进行测试，以表明重新灌装NPG 这个装置并不难，并表明我们可以麻醉神经长达6个月。这些步骤将 这对于构建可用于延长患者疼痛缓解的NPG结构至关重要。

7. Project Summary/Abstract It is estimated that by 2050 there will be some 3.6 million Americans living with limb loss, that is, an amputated extremity. Unfortunately, most of these patients will experience chronic post-amputation pain (CPAP), which has been found to occur in up to 80% of patients for up to 20 years after their amputation. CPAP can be felt either in the stump of the missing limb (residual limb pain, or stump pain) or it can be felt as if the missing limb were still there (phantom limb pain). As yet there exists no consensus recommended therapy for such pain, and treatments that are available (including opioid and other medications) are frequently inadequate to achieve good pain control. Some studies have observed that delivering an anesthetic agent directly to the injured nerves in an amputation stump can prevent the onset of CPAP or even, in some patients, effectively suppress CPAP. This may be a promising line of therapy but is difficult for patients to manage: it involves placement of a catheter through the skin into the sheath of the nerve, through which there is a constant flow of anesthetic drug in fluid, driven by an infusion pump that has to be constantly ported about. A better means of delivering anesthetic directly to injured nerves over the long-term that wasn't so cumbersome would be a significant advance. We now propose to develop a device that is capable of accomplishing this task: the Novaflux PainGuard (NPG). NPG constructs are derived from FDA-approved dialysis technology; they are comprised of meshed fibers that contain micro-perforations. The mesh/fibers can be loaded with an anesthetic drug in very high quantities, which will then slowly leach out into its surroundings. NPG devices can be placed surgically around injured nerves at the time of amputation, such that the anesthetic within the NPG numbs the nerves continuously as it exits the PainGuard device. Moreover, NPG devices can be attached to a filling port that is also placed under the skin; this port can be used to re-fill the NPG in an office visit with a simple injection (similar to a vaccination shot, but directly into the port under the skin). This can allow the NPG to function for very long periods of time, for many months or even years with re-charging, potentially even a lifetime. In this proposal our goal is to engineer NPG devices that will have the maximum effect on pain control for the longest period of time without needing a re-fill. We will vary and test different design features of the NPG, including the size and density of the micro-perforations, the use of “wetting agents” to facilitate (or extend) release of the anesthetic drug, etc. We will test the most promising NPG designs in a rat model of nerve injury to the leg, and show that we can achieve at least a month's worth of pain relief at a single charge. We will then build a larger version of the NPG with a filling port attached and test it in rabbits, to show that re-filling the NPG device is not difficult, and to show that we can anesthetize the nerves for up to 6 months. These steps will be crucial to building NPG constructs that can be used for extended pain relief in patients.