Targeted Muscle Reinnervation (TMR) at Time of Major Amputation Decreases Phantom and Residual Limb Pain

Background: A growing population of young soldiers returning from military conflict and civilians suffering from diabetes, peripheral vascular disease, and cancer contribute to the nearly two million people living with limb loss in the United States alone. A surprising majority of amputees suffer from chronic pain in the form of unpredictable neuroma-related residual limb and phantom limb pain. These conditions profoundly decrease patient function and quality of life, and despite a myriad of proposed therapies, there are no reliable treatment or prevention strategies for postamputation pain. Targeted muscle reinnervation (TMR) surgically transfers amputated nerves to redundant motor nerves to allow for physiologic nerve healing. In this study, TMR was proposed for prevention of postamputation pain. Methods: Immediate TMR was performed in 51 patients undergoing major limb amputation as a preemptive measure for symptomatic neuromas and phantom limb phenomena at two centers. Pain outcomes were assessed using an eleven-point Numerical Rating Scale (NRS) and the Patient-Reported Outcomes Measurement Information System (PROMIS), and were compared to a cross-section of 438 untreated amputee controls. Opioid prescription patterns were secondarily collected for TMR patients. Findings: Patients undergoing TMR concurrently at the time of major limb amputation had less phantom limb and residual limb pain compared to untreated amputee controls across all subgroups and by all measures. Median "worst pain in the past 24 hours" for the TMR cohort was 1 out of 10 compared to 5 (phantom) and 4 (residual) out of 10 in the general amputee population for phantom and residual limb pain (p=0.003 and p<0.001, respectively). Forty-five percent of TMR patients reported zero phantom limb pain, and 49.2% reported zero residual limb pain compared to approximately 20% for each in the general amputee cohort. Median PROMIS t-scores were lower in TMR patients than general amputee participants for both phantom limb pain: Pain Intensity (36.3 versus 48.3), Pain Behavior (50.1 versus 56.6), Pain Interference (40.7 versus 55.8) and residual limb pain: Pain Intensity (30.7 versus 46.8), Pain Behavior (36.7 versus 57.3), Pain Interference (40.7 versus 57.3). TMR was associated with 3.03 (phantom) and 3.92 (residual) times higher odds of decreasing pain severity compared to general amputee participants. Interpretation: Preemptive surgical handling of amputated nerves by targeted muscle reinnervation at the time of limb loss should be strongly considered for prevention of pathologic phantom limb pain and symptomatic neuroma-related pain. Funding Statement: This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Orthopaedic Research Program under Award No. W81XWH-13-2-0100. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. No authors were paid to write this article by a pharmaceutical company or other agency. The corresponding author, Ian L. Valerio, has full access to all the data in the study and had final responsibility for the decision to submit for publication. Declaration of Interests: None of the authors in this manuscript have any conflicts of interest. Ethics Approval Statement: This work was approved by The Ohio State University Institutional Review Board (Protocol Number 2017C0150). This work was approved by the Northwestern University Institutional Review Board (Protocol Number STU00205866).