Distinct neurotoxic effects of select local anesthetics on facial nerve injury and recovery

Restor Neurol Neurosci. 2020;38(2):173-183. doi: 10.3233/RNN-190987.

Abstract

Background: Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve.

Objective: To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve.

Methods: This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury.

Results: FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days).

Conclusions: Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.

Keywords: Neurotoxicity; facial nerve injury; liposomal bupivacaine; local anesthetic toxicity; motoneuron survival; peripheral nerve block; peripheral nerve injury; regional anesthesia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anesthetics, Local / pharmacology*
  • Animals
  • Bupivacaine / pharmacology*
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Facial Nerve / drug effects
  • Facial Nerve / physiopathology
  • Facial Nerve Injuries / drug therapy*
  • Male
  • Mice, Inbred C57BL
  • Motor Neurons / drug effects
  • Peripheral Nerve Injuries / drug therapy*

Substances

  • Anesthetics, Local
  • Bupivacaine