Article Text

Download PDFPDF
Physiologic Mechanisms by Which Local Anesthetics May Cause Injury to Nerve and Spinal Cord
  1. Michael W. Kalichman, Ph.D.
  1. From the Departments of Anesthesiology and Pathology, University of California, San Diego, and the Veterans Administration Medical Center, San Diego, California.
  1. Address correspondence and reprint requests to Michael W. Kalichman, Ph.D., Departments of Anesthesiology and Pathology (9151), University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-9151.


Objective. Review evidence for possible physiologic mechanisms by which local anesthetics cause nerve injury was reviewed.

Methods. Published clinical case reports, and both in vivo and in vitro experimental studies in animals, were reviewed. Reports with direct bearing on possible mechanisms of local anesthetic neurotoxicity were included.

Results. There is basic and clinical evidence that local anesthetics can cause nerve injury. Nerve injury may result from direct toxicity to the axon or Schwann cell, or may be secondary to disruption of the nerve microenvironment. Although each of these possibilities is supported by published experiments, injury to the axon is the most likely explanation for persistent neurologic deficits, such as those believed to result from clinical use of local anesthetics. Whether the injury is direct or indirect, and the precise mechanism by which it occurs, has received only limited study.

Conclusions. In rare instances, the clinical use of local anesthetics is associated with neurologic morbidity. The physiologic mechanisms of toxicity for which there is the best evidence are inhibition of fast axonal transport, disruption of the axonal cytoskeleton, axonal degeneration, and ischemic nerve injury. The effects of local anesthetics on nerve blood flow may be related to inhibition of endothelium-dependent vasodilation or interruption of the synthesis of vasodilating prostaglandins. Both the prevention and the treatment of nerve injury caused by local anesthetics requires information that is not yet available about the physiologic and molecular mechanisms for direct neural toxicity of local anesthetics.

  • Local anesthetics
  • peripheral nerve
  • ischemia
  • spinal cord.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Supported by the Office of Research and Development (Medical Research Service) of the Department of Veterans Affairs and by U.S. Public Health Service Grant NS24833.