A fully-implanted spinal cord stimulation system to restore sensation and relieve phantom limb pain after lower-limb amputation - in the united states, over 1.5 million people live with lower-limb…

The University of Pittsburgh received a $3.24M Cooperative Agreement from the National Institute of Neurological Disorders and Stroke (NINDS) under the Drug Use and Addiction Research Programs (CFDA 93.279), awarded September 1, 2025, through August 31, 2027. This award supports the development and clinical evaluation of a fully implanted spinal cord stimulation (SCS) system designed to restore sensory sensation and alleviate phantom limb pain (PLP) in individuals with lower-limb amputation (LLA). The research addresses a significant clinical need, as over 70% of the 1.5 million Americans living with LLA experience PLP, with approximately 30% becoming chronic opioid users.

The project delivers clinical research services through a two-phase investigation utilizing a crossover study design conducted at the University of Pittsburgh's Pennsylvania facility. During the UG3 phase (months 1-24), the institution will obtain FDA and Institutional Review Board approvals, followed by a nine-month at-home evaluation comparing the fully implanted SCS system with traditional SCS treatment. Concurrently, the research team will employ advanced neuroimaging techniques to quantify changes in brain representations of the lower limb associated with PLP relief, exploring whether somatosensory restoration reverts pain-related neural changes. The deliverables encompass safety and feasibility data from human subjects, regulatory approvals, and neuroscientific evidence regarding the mechanism by which wireless sensory neuroprosthetics can reduce or eliminate phantom limb pain through sensory feedback restoration.

A fully-implanted spinal cord stimulation system to restore sensation and relieve phantom limb pain after lower-limb amputation - in the united states, over 1.5 million people live with lower-limb amputation (LLA). Over 70% of people with LLA experience phantom limb pain (PLP), with 50% experiencing "high intensity" pain and 25% describing the pain as disabling. Opioid prescriptions among people with PLP are common, with one study showing nearly 30% of people that underwent an amputation exhibiting chronic opioid consumption. While scientific understanding of the mechanisms of PLP is limited, evidence suggests that the loss of sensory feedback after amputation contributes to development of PLP. There is growing evidence that neuroprostheses that restore somatosensation after amputation can reduce or completely alleviate PLP. For example, recent studies in our lab demonstrated that spinal cord stimulation (SCS) via percutaneously implanted leads can evoke sensations in the missing limb and reduce PLP. Widespread clinical adoption will require fully implanted systems that communicate wirelessly with external sensors on the prosthesis, allowing US to explore long-term at-home use of somatosensory neuroprostheses. The primary goal of this project is to quantify the safety and feasibility of a fully implanted SCS system to treat PLP by restoring sensation from the missing foot in people with LLA. Using a cross-over design, we will quantify changes in PLP while subjects with LLA use the system at home for 9 months, as compared to changes in PLP they experience with traditional SCS. Additionally, using cutting edge neuroimaging techniques, we will explore if there are changes in brain representations of the lower limb associated with PLP and whether those changes are reverted in subjects that experience pain relief via somatosensory restoration. UG3 phase (months 1-24) aim 1: obtain FDA and IRB approval for a study of sensory restoration to treat PLP in people with LLA we will perform biocompatibility and large-animal GLP studies in support of an IDE application for a one-year trial of a fully implanted SCS system to restore somatosensation and reduce PLP. Aim 2: quantify changes in cortical representation of the lower limb in people with phantom limb pain we will perform magnetoencephalography studies in 10 people with LLA with PLP, 10 people with LLA without PLP, and 10 able-bodied controls to quantify changes in cortical representations that are associated with PLP. UH3 phase (months 25-60) aim 3: test safety and efficacy of somatosensory restoration for reducing phantom limb pain during a one-year implantation period, six subjects with LLA and PLP will progress through a randomized cross- over study in which they receive traditional, paresthesia-based SCS for six weeks and real-time somatosensory restoration for nine months, separated by a one-month washout period.