Targeted Muscle Reinnervation: Neuroma Prevention - Rehabilitation Institute of Chicago

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Targeted Muscle Reinnervation: A Neural Interface for Artificial Limbs

Targeted Muscle Reinnervation: A Neural Interface for Artificial Limbs (CRC Press, 2013) can be purchased at the CRC Press website or on Amazon.

RIC Center for Bionic Medicine

TMR research was pioneered at the Center for Bionic Medicine (CBM). The CBM combines science, engineering, and clinical skill to improve function and life quality for persons with limb loss.

Development of this website was supported by the National Library of Medicine of the National Institutes of Health, Award Number G13LM011221. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Targeted Muscle Reinnervation as a Strategy for Neuroma Prevention

Neuroma Prevention

TMR as a Strategy for Neuroma Prevention

Median nerve end-neuroma encountered during a
transhumeral TMR procedure. (Click image to enlarge)

People with amputations must often live with neuromas, benign yet painful growths of nerve tissue that develop at the end of severed nerves. Consisting of disorganized axons encased in scar and fibrous tissue, neuromas cause a focal pain that is often difficult to treat.

Neuroma pain is caused by: (1) mechanical or chemical irritation of axons in the neuroma and (2) spontaneous firing within the neuroma and retrograde axonal sprouts proximal to the neuroma.

People with neuromas often feel pain when they wear prostheses, which can put pressure on neuromas and create intense discomfort. As a result, neuroma pain can interfere with a person’s ability to comfortably wear and use a prosthesis.

Between 10 to 25% of individuals with major limb amputations will develop chronic localized pain as a result of symptomatic neuromas. Neuroma pain is reported in as many as 71% of individuals who have had a traumatic amputation [1-4].

View how TMR could prevent or treat neuromas.

Many strategies have been investigated to either stop neuroma formation or ease the resulting pain, including pharmacologic treatments, modification of the prosthesis, scar massage, surgery, and manipulation of the bone or soft tissues. Unfortunately, these treatments may be temporary and ineffective, as proximal axons inevitably form another neuroma [5].

TMR may prevent or reduce neuroma formation by providing a denervated muscle target for the transected nerves to grow into. TMR allows regenerating axons to grow into the target muscle instead of forming a neuroma. In other words, TMR gives the severed nerves somewhere to go and something to do.


  1. Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain. Nov 1983;17(3):243-256.

  2. Jensen TS, Krebs B, Nielsen J, Rasmussen P. Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain. Pain. Mar 1985;21(3):267-278.
  3. Ducic I, Mesbahi AN, Attinger CE, Graw K. The role of peripheral nerve surgery in the treatment of chronic pain associated with amputation stumps. Plastic and reconstructive surgery. Mar 2008;121(3):908-914; discussion 915-907.
  4. Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted Muscle Reinnervation: A Novel Approach to Postamputation Neuroma Pain. Clinical orthopaedics and related research. Feb 22 2014.
  5. Guse DM, Moran SL. Outcomes of the surgical treatment of peripheral neuromas of the hand and forearm: a 25-year comparative outcome study. Annals of plastic surgery. Dec 2013;71(6):654-658.

Clinical Evidence

Evidence that TMR may prevent neuroma formation

Typical Neuroma After TMR(Click image to enlarge)

The effects of TMR on controlling and preventing neuroma pain were first evaluated in animal models and findings were later supported through clinical observation.

Preclinical Studies

  • In a rabbit neuroma model, previously amputated nerve stumps were transferred to a denervated rectus abdominus flap, after excision of end neuromas. After 10 weeks, the histological morphology of transferred nerves resembled non-amputated nerve controls more closely than amputated nerves with neuromas, suggesting that TMR prevented reformation of end neuromas [1].
  • In a rat hind limb model, mixed (sensory + motor) or sensory nerves were transferred to either: (A) the motor point of a denervated target muscle (analogous to a TMR procedure); (B) the motor point of an innervated target muscle; or (C) buried in muscle. After 16 weeks, histological and gross anatomical comparisons for both types of nerves indicated that transfer to the motor point of a denervated muscle (group A) significantly reduced neuroma formation.

Initial Clinical Evidence

  • Following TMR procedures at Northwestern Memorial Hospital (NMH), five out of nine shoulder disarticulation patients who reported neuroma pain prior to their TMR procedure reported no neuroma pain after TMR.
  • At the Harborview Medical Center at the University of Washington in Seattle, 20 patients reported feeling neuroma pain prior to TMR; however, after TMR surgery, none of these patients reported neuroma pain.
  • In a retrospective study analyzing data from NMH and the San Antonio Military Medical Center (SAMMC), of 15 patients with neuroma pain before TMR, 14 experienced complete resolution of pain in the transferred nerves [2].
  • In individuals who did report continued neuroma pain following TMR surgery, the source of the pain in 2 out of 3 individuals was the lateral antebrachial cutaneous nerve, which was not transferred to muscle during the TMR procedures. In the third patient, the neuroma pain was reduced, although not eliminated, by TMR surgery.

These results suggest that TMR may be a new surgical option to prevent neuroma formation or to treat existing neuromas.

In order to further research the benefits of TMR in preventing and treating neuroma pain, Dr. Gregory Dumanian is leading a $2.45 million clinical trial funded by the U.S. Department of Defense's Congressionally Directed Medical Research Programs (CDMRP) Peer-Reviewed Orthopaedic Research Program (PRORP) Clinical Trial Award (Award # W81XWH-13-2-0100). This study will compare TMR with the current gold standard for surgical neuroma treatment—burying the severed nerve in muscle. Read more about that research effort– which involves collaboration with Northwestern Memorial Hospital, San Antonio Military Medical Center, Walter Reed National Military Medical Center, and the University of Washingtonhere (PDF).


  1. Kim PS, Ko JH, O'Shaughnessy KK, Kuiken TA, Pohlmeyer EA, Dumanian GA. The effects of targeted muscle reinnervation on neuromas in a rabbit rectus abdominis flap model. The Journal of hand surgery. Aug 2012;37(8):1609-1616.
  2. Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted Muscle Reinnervation: A Novel Approach to Postamputation Neuroma Pain. Clinical orthopaedics and related research. Feb 22 2014.

Further Reading

Further Reading

Traumatic Neuromas (2010) InMotion (Amputee Coalition).

Recent Reviews

Watson J, Gonzalez M, Romero A, Kerns J. Neuromas of the hand and upper extremity. The Journal of hand surgery. Mar 2010;35(3):499-510.

Brogan DM, Kakar S. Management of neuromas of the upper extremity. Hand clinics. Aug 2013;29(3):409-420.



Jason Ko, MDJason H. Ko, MD, received a BS in Economics with minors in Philosophy and Chemistry, and an MD from Duke University. Dr. Ko completed an integrated residency in plastic and reconstructive surgery at Northwestern University Feinberg School of Medicine, and a fellowship in hand and microvascular surgery at the University of Washington, Seattle, WA. Dr. Ko is an Assistant Professor in the Division of Plastic Surgery within the Department of Surgery, and in the Department of Orthopedics and Sports Medicine, at the University of Washington, WA, specializing in hand and upper extremity surgery, brachial plexus and peripheral nerve surgery, and reconstructive microsurgery. Dr. Ko has performed several preclinical animal studies examining the effects of TMR on neuroma formation and has performed numerous TMR procedures.

Peter S. Kim, MDPeter S. Kim. MD, received an AB in Human Biology and an MD from Brown University's Program in Liberal Medical Education. After completing an integrated plastic and reconstructive surgery residency at Northwestern University Feinberg School of Medicine, Dr. Kim completed a training fellowship in surgery of the hand, upper extremity, and microsurgery at the University of Washington, Department of Orthopedics and Sports Medicine, Seattle, WA. Dr. Kim is currently an Instructor in Surgery at Harvard Medical School and operates at New England Baptist Hospital, where he specializes in hand, upper extremity, and reconstructive microsurgery. Dr. Kim has participated in numerous TMR procedures and has created a preclinical amputation model to investigate the effects of TMR on neuroma formation.

Douglas G. Smith, MDDouglas G. Smith, MD, received his MD from the Pritzker School of Medicine, University of Chicago. Dr. Smith completed a residency in orthopedic surgery and rehabilitation at Loyola University Medical Center, Maywood, IL, and a fellowship in foot, ankle and amputation surgery at Harborview Medical Center, University of Washington, Seattle, WA. Dr. Smith is a Professor in the Department of Orthopedics and Sports Medicine at the Harborview Medical Center and University of Washington, WA, specializing in general orthopedic trauma and in surgery and rehabilitation for amputees, and has served as a consultant to the United States Military Amputee Centers from 2002 to the present. Dr. Smith has performed more than 40 TMR procedures in the acute, sub-acute, and chronic amputation settings, with a specific interest in the effects of TMR on pain.