Comparing electrical stimulation and tacrolimus (FK506) to enhance treating nerve injuries

Muscle Nerve. 2019 Nov;60(5):629-636. doi: 10.1002/mus.26659. Epub 2019 Aug 21.


Introduction: Neuroenhancing therapies are desired because repair of nerve injuries can fail to achieve recovery. We compared two neuroenhancing therapies, electrical stimulation (ES) and systemic tacrolimus (FK506), for their capabilities to enhance regeneration in the context of a rat model.

Methods: Rats were randomized to four groups: ES 0.5 mA, ES 2.0 mA, FK506, and repair alone. All groups underwent tibial nerve transection and repair, and outcomes were assessed by using twice per week walking track analysis, cold allodynia response, relative muscle mass, and nerve histology.

Results: Electrical stimulation and FK506 groups demonstrated improved functional recovery and myelinated axon counts distal to the repair compared with repair alone. Electrical stimulation provided improvements in nerve regeneration that were not different from optimized FK506 systemic administration.

Discussion: Providing ES after nerve repair improved regeneration and recovery in rats, with minimal differences in therapeutic efficacy to FK506, further demonstrating its clinical potential to improve management of nerve injuries.

Keywords: FK506; electrical stimulation; functional recovery; peripheral nerve; regeneration; tacrolimus; tibial nerve.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation / methods*
  • Immunosuppressive Agents / pharmacology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neurosurgical Procedures
  • Peripheral Nerve Injuries
  • Rats
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Tacrolimus / pharmacology*
  • Tibial Nerve / injuries*
  • Tibial Nerve / pathology
  • Tibial Nerve / surgery


  • Immunosuppressive Agents
  • Tacrolimus