Project Summary The lack of effective pain treatments has catalyzed the opioid epidemic in America, causing an estimated 93,000 deaths in 2020, calling for more effective and non-opioid based management. One alternative pain treatment is via nerve stimulators, which are devices placed near a peripheral nerve or on the spinal cord and use electrical signals to modulate the perception of pain. Most nerve stimulators are surgically implanted and made of permanent metal wires. A pulse generator and battery pack are also surgically implanted under the skin. These devices can provide effective pain relief to patients, but have excessively high complication rates of 30-40%, resulting from the wire moving, breaking, not working, or the implantable battery pack or permanent wire causing new sites of pain. These complications require yet another surgery to correct the problem, increasing costs for the patient and the healthcare system. Temporary nerve stimulators can mitigate some of the complications, but these are made of permanent materials and must be removed after 60 days, while the removal causes 10- 15% lead fracture leaving the lead permanently in the body. Vanish Therapeutics proposes a bioresorbable, non- surgical peripheral nerve stimulator to treat chronic pain. Once inserted, the device will provide electrical stimulation for up to 60 days, after which it will be safely degraded by applying an anodic electrical stimulus resulting in resorption by the body, eliminating the need for any revision surgeries. This Phase I project will establish feasibility and produce safety/efficacy data for a Phase II application. Towards this goal, we will 1) Develop the minimally invasive stimulation lead composed of entirely bioresorbable components. The electrochemical properties and degradation profile will be characterized and optimized to meet the application needs. Stimulation will be tested in physiological saline solution, and the electrode must be capable of delivering at least 550,000,000 stimulation pulses, equivalent to 60 days of full-time clinical stimulation. The degradation of the device will then be accelerated with an anodic electrical stimulus. The toxicity of the material/device and degradation products will be evaluated following ISO standards. 2) Design the wearable external pulse generator with programmable stimulation current profiles and an active impedance measurement circuit. The device will deliver the electrical stimulations for pain relief and drive the degradation of the wire after the end of stimulation. 3)Validate the stimulation efficacy and degradation safety of the integrated stimulator in a rat neuropathic pain model. Using the previously developed pulse generator and injectable electrode, animals will be stimulated for 60 days, with weekly electrochemical and electrophysiological measurements to monitor the electrode function. After stimulation, the electrode will be subjected to electrically driven degradation, resulting i...