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Chi et al. Plast Aesthet Res 2023;10:56 Plastic and
DOI: 10.20517/2347-9264.2023.48
Aesthetic Research

Review Open Access

Therapeutic strategies for peripheral nerve injuries:
FK506 and electrostimulation

David Chi , Erin C. Silverman, Evan B. Marsh, Matthew D. Wood, Susan E. Mackinnon

Department of Surgery, Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO
63110, USA.
Correspondence to: Prof. Susan E. Mackinnon, Division of Plastic and Reconstructive Surgery, Department of Surgery,
Washington University School of Medicine, 660 S. Euclid Ave, Saint Louis, MO 63110, USA. E-mail: mackinnons@wustl.edu
How to cite this article: Chi D, Silverman EC, Marsh EB, Wood MD, Mackinnon SE. Therapeutic strategies for peripheral nerve
injuries: FK506 and electrostimulation. Plast Aesthet Res 2023;10:56. https://dx.doi.org/10.20517/2347-9264.2023.48
Received: 31 May 2023 First Decision: 21 Aug 2023 Revised: 13 Sep 2023 Accepted: 25 Sep 2023 Published: 12 Oct 2023

Academic Editor: Samuel O. Poore Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
Efficacious therapeutics for peripheral nerve injuries remain incompletely described in the literature. However, over
the last several decades, delivery of FK506 (Tacrolimus) and electrostimulation have demonstrated great promise
for supplementing surgical advances in treating peripheral nerve injuries. This review describes the discovery,
mechanistic investigations, and clinical translation of these strategies to promote functional recovery. FK506 has
demonstrated the ability to increase the regeneration rate after nerve injury by a variety of hypothesized
mechanisms, yet clinical utility remains limited due to systemic immunosuppression. Local administration of
FK506 continues to be an active area of inquiry for minimizing side effects while maintaining its neuroregenerative
effects. Electrostimulation of a nerve proximal to the site of surgical nerve repair has demonstrated increased
axonal regeneration and accelerated recovery of both motor and sensory nerves. In addition, electrostimulation
also appears to improve axon matching during reinnervation from motor to motor and sensory to sensory
pathways and is used clinically in our surgeries. However, the specific parameters to best incorporate
electrostimulation into the operating theater are still evolving. Utilizing translational rodent and murine models,
surgical techniques and these therapeutic strategies have gradually become more viable as safety profiles and
mechanisms are gradually understood. This review presents the state of the field for these therapeutic avenues and
discusses further areas of research.

Keywords: Electrical stimulation, FK506, peripheral nerve, nerve regeneration

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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