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

Gregory A. Dumanian*, Benjamin K. Potter, Lauren M. Mioton, Jason H. Ko, Jennifer E. Cheesborough, Jason M. Souza, William J. Ertl, Scott M. Tintle, George P. Nanos, Ian L. Valerio, Todd A. Kuiken, A. Vania Apkarian, Kyle Porter, Sumanas W. Jordan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

311 Scopus citations


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:NCT 02205385 at

Original languageEnglish
Pages (from-to)238-246
Number of pages9
JournalAnnals of surgery
Issue number2
StatePublished - 1 Aug 2019
Externally publishedYes


  • neuroma
  • phantom limb pain
  • postamputation pain
  • randomized clinical trial
  • targeted muscle reinnervation


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