Related Experiment Video
Updated: Oct 4, 2026
Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain
Published on: March 8, 2024
Primary versus secondary targeted muscle reinnervation in amputees: A long-term comparative analysis of pain
Floris V Raasveld1, Maximilian Mayrhofer-Schmid2, Otis C van Varsseveld3
1Division of Plastic and Reconstructive Surgery, Department of General Surgery, Massachusetts General Hospital, Harvard University, Boston, MA, United States; Hand and Arm Center, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Department of Plastic, Reconstructive and Hand Surgery, Erasmus Medical Center, Erasmus University, Rotterdam, the Netherlands.
Introduction:
Targeted muscle reinnervation (TMR) has emerged as an effective intervention for neuropathic pain management in amputees; however, long-term comparative data between primary (prophylactic) and secondary (therapeutic) approaches continue to be 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, whereas 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 and 103 sTMR, median follow-up: 2.5 years (IQR: 1.8-3.8 years)). Long-term pain mitigation achievement rates were comparable between the 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 achieving 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:
Although long-term outcomes appear to be similar between pTMR and sTMR, pTMR is associated with faster achievement of pain relief. These findings support prophylactic TMR when feasible while providing reassurance that delayed intervention is effective, with important implications for patient counseling and clinical decision-making.
Level Of Evidence:
III - Therapeutic.
