TMR and RPNI Sustainably Reduce Long-Term Pain and Opioid Use after Oncologic Amputation: A Comparison With Untreated Amputees

INTRODUCTION: Chronic postamputation pain, driven by residual limb pain (RLP) and phantom limb pain (PLP), is a major source of long-term disability after limb loss. The long-term effectiveness of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), particularly compared with untreated patients, remains unclear. METHODS: A retrospective cohort study was performed at a single quaternary cancer center. Adult oncologic amputees who received TMR and/or RPNI were compared with a historic cohort without nerve reconstruction, with outcomes assessed at least 10 months after amputation. Long-term pain and controlled-substance use were evaluated using patient-reported measures (Numeric Pain Scale, PROMIS Pain Intensity, Interference, and Behavior) and prescription records for opioids, benzodiazepines or pregabalin, and gabapentin. RESULTS: Seventy-nine patients were analyzed (25 historic, 54 TMR/RPNI). At long-term follow-up, the TMR/RPNI cohort had significantly lower RLP (0.0 [0.0-2.0] vs. 2.0 [0.0-4.0], p = 0.017), PLP (0.0 [0.0-3.0] vs. 4.0 [2.0-5.0], p = 0.001), and PROMIS Pain Intensity (47.5 [36.3-58.5] vs. 54.8 [51.4-61.9], p = 0.040) and Behavior (56.9 [45.5-62.4] vs. 64.5 [59.8-68.5], p = 0.003) scores. Opioid (p = 0.022) and benzodiazepine or pregabalin (p = 0.017) use were significantly reduced, while gabapentin use was higher (p = 0.006), indicating a transition to non-opioid analgesia. CONCLUSION: This study provides the long-term comparison of oncologic amputees with and without TMR/RPNI and demonstrates durable reductions in pain and opioid dependence more than 10 months after amputation. Physiologic nerve reconstruction offers sustained benefit and supports improved survivorship and safer analgesic practices in oncologic amputation care.