Novel Implantable Device to Negate Post-Amputation Pain

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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.