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

Ann Surg. 2019 Aug;270(2):238-246. doi: 10.1097/SLA.0000000000003088.


Objective: To compare targeted muscle reinnervation (TMR) to "standard treatment" of neuroma excision and burying into muscle for postamputation pain.

Summary background data: To date, no intervention is consistently effective for neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.

Methods: A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0-10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.

Results: In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus -0.2 (difference 3.4, adjusted confidence interval (aCI) -0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI -0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment [mean (aCI) = 3.5 (0.6, 6.3), P = 0.03]. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.

Conclusions: In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.

Trial registration: NCT02205385 at

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Amputation, Surgical / rehabilitation*
  • Amputees / rehabilitation*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Muscle, Skeletal / innervation*
  • Nerve Transfer / methods*
  • Neuroma / surgery*
  • Pain Measurement
  • Pain, Postoperative / diagnosis
  • Pain, Postoperative / surgery*
  • Phantom Limb / surgery*
  • Plastic Surgery Procedures / methods
  • Prospective Studies
  • Single-Blind Method

Associated data