An innovative device for management of neuropathic pain after spinal cord injury Neuropathic pain (NP) after spinal cord injury (SCI) is common and debilitating, and has increasingly been recognized as an important contributor to suffering, poor rehabilitation outcomes and reduced quality of life. Different non-invasive neurodomulatory techniques via peripheral (TENS) or central (tDCS) electrical stimulation have been used. However, their effectiveness is still limited and controversial. We have recently developed a novel, non- invasive, non-pharmacological intervention – Breathing-controlled electrical stimulation (BreEStim) for neuropathic pain management. Our preliminary work has shown that that BreEStim could produce effective analgesic effects in SCI+NP patients via central neuromodulation mechanisms. Though clinically effective, the BreEStim apparatus is currently a customized apparatus for laboratory use only. A stand-alone BreEStim device is needed for routine clinical use. The planned BreEStim device will be developed by our industry partner, Soterix Medical Inc (SMI). The device will then be tested in a single-center randomized controlled clinical trial at our research center. Accordingly, we would like to pursue the following specific aims. UG3 Specific Aim 1: Develop an integrated BreEStim device under FDA Quality Systems UH3 Specific Aim 2: Examine efficacy and safety of BreEStim in a single-center randomized controlled clinical trial UH3 Specific Aim 3: Iterate device hardware, obtain IEC certification, and advance regulatory process. At the completion of this project, pending promising clinical outcome, the results will establish that the developed BreEStim device is safe and effective. We will accordingly engage the FDA on the evidence needed to support the intended use. If a larger multicenter trial is necessary for marketing clearance, we will engage the FDA about trial design and pathway for approval. UTHealth and SMI have reached an agreement to facilitate product development, IP acquisition, translation and commercialization.

The overall goal of this project is to translate a laboratory-based apparatus and method into a stand-alone BreEStim device and to validate its clinical efficacy and safety for neuropathic pain management in people after spinal cord injury (SCI) in a single-center randomized controlled clinical trial. At the completion of this project, we will be able to provide evidence that the BreEStim device is safe and effective for chronic neuropathic pain management in patients after spinal cord injury.