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Primary vs. Secondary Targeted Muscle Reinnervation in Amputees: A Long-Term Comparative Analysis of Pain Trajectories
Maximilian Mayrhofer-Schmid, MD
1, Otis van Varsseveld, MD
2, Floris V. Raasveld, MD
3, Benjamin R Johnston, MD, PhD
4, Anna Luan, MD, MS
5, David Hao, MD
2, Ian L Valerio, MD, MS, MBA
6; Kyle R. Eberlin, MD
6(1)BG Klinikum Unfallkrankenhaus Berlin, Berlin, Berlin, Germany, (2)Massachusetts General Hospital/ Harvard Medical School, Boston, MA, (3)Massachusetts General Hospital/Harvard Medical School, Boston, MA, (4)MGH, Boston, MA, (5)Stanford University, Palo Alto, CA, (6)Massachusetts General Hospital | Harvard Medical School, Boston, MA
Introduction: Targeted muscle reinnervation (TMR) has emerged as an effective intervention for neuropathic pain management in amputees, but long-term comparative data between primary (prophylactic) and secondary (therapeutic) approaches remain limited.
Methods: This prospective longitudinal study analyzed amputee patients over a 5-year follow-up period (minimum follow-up:12 months). Primary TMR (pTMR) was performed ?14 days post-amputation, while secondary TMR (sTMR) was performed >14 days post-amputation. Pain trajectories were modeled using multilevel mixed-effects models with natural splines. Pain mitigation was defined as achieving pain scores ?3/10 for ?3 months (pTMR) or ?3-point reduction (minimal clinically important difference, MCID) or scores ?3/10 for ?3 months (sTMR).
Results: The study included 204 patients (101 pTMR, 103 sTMR, median follow-up: 2.6 years (IQR:2.1-3.2)). Long-term pain mitigation achievement rates were comparable between groups (66% primary (95%CI:56.5-75.2%) vs. 69% secondary (95% CI: 59.2-77.6%), p=0.681). The median time to achieve pain mitigation was 5.4 months for pTMR versus 12.9 months for sTMR (p<0.001) (pTMR:2.4 times faster). At 6 months, pTMR patients had 3.12 times higher odds of achieving sustained relief (95% CI: 1.61-6.24, p<0.001). Statistically significant differences in pain scores favored pTMR through 18 months, with peak differences of 1.52 points at 6 months (p<0.001). No significant differences existed beyond 18 months.
Conclusions: While long-term outcomes appear to be similar between primary and secondary TMR, primary TMR confers a clear advantage in the time to pain relief
. These findings support prophylactic TMR when feasible while providing reassurance that delayed intervention remains effective, with important implications for patient counseling and clinical decision-making.
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