Targeted Muscle Reinnervation Successfully Treats Neuroma Pain and Phantoms in Major Limb Amputees: A Randomized Clinical Trial

Background: A majority of amputees suffer from pain isolated to the residual limb or pain perceived in the missing limb, known as phantom limb pain. End-neuromas are the leading cause of residual limb pain while the etiology of phantom limb pain is much more complex and less well understood. There are over 150 surgical treatments for end-neuromas in the literature, highlighting the fact that no single treatment consistently works. Targeted Muscle Reinnervation (TMR) is a surgical procedure first developed to provide intuitive prosthesis control by transferring cut nerve endings to otherwise redundant motor nerves. It was incidentally found that patients undergoing TMR also had improvement in residual limb and phantom limb pain post-operatively. The objective of this randomized clinical trial is to compare TMR as a treatment option for amputee-related pain to the current standard of care for end-neuromas, which entails neurectomy and muscle-burying.

Methods: A total of 28 major limb amputees suffering from neuroma-related pain were randomized to either standard therapy (14 patients, 15 limbs) or Targeted Muscle Reinnervation (14 patients, 15 limbs) across two sites. Three standard therapy patients converted to TMR one year after their initial intervention and were included in the TMR cohort as well, leaving a total of 18 limbs in final analysis. Pre-operative and post-operative pain outcomes were assessed using an eleven-point Numerical Rating Scale.

Results: With an average follow up of almost 18 months, patients undergoing TMR had a significant reduction in both phantom limb and residual limb scores compared to pre-operative values. Specifically, average phantom pain levels decreased from 5.7 (0-10 scale) pre-operatively to 1.8 post-operatively, and average residual limb pain decreased from 6.7 pre-operatively to 3.4 post-operatively (all p<0.05). Standard treatment failed to yield any significant improvement in phantom pain (3.9 pre-operative vs 4.3 post-operative) with only minimal improvement in residual limb pain values (6.9 pre-operatively versus 5.7 post-operatively, p>0.05). The percentage of patients who had no phantom pain (NRS score of zero) increased from 16.7% to 50% in the TMR cohort. There were few individuals free from residual limb pain before or after surgery in either intervention arm. The percentage of individuals dealing with mild pain (NRS score 1-3) increased from 0% to 66.7% in the TMR cohort. Conversely, the number of individuals suffering from severe phantom limb or severe residual limb pain (NRS 7-10) increased in the standard treatment arm post-operatively. The trial was ultimately stopped in light of the noted failures and lack of overall improvement seen in the standard arm.

Conclusion:

Results from this randomized clinical trial reveal that Targeted Muscle Reinnervation provides profound long-term improvement in phantom limb pain and residual limb pain in major limb amputees. TMR should be the treatment of choice for chronic pain in amputees as the results from standard therapy were disappointing for patient outcomes.