Prolonged alleviation of tactile allodynia by intravenous lidocaine in neuropathic rats

Anesthesiology. 1995 Oct;83(4):775-85. doi: 10.1097/00000542-199510000-00017.


Background: Lidocaine may be useful in the treatment of neuropathic pain states. The authors hypothesized that lidocaine would reduce tactile allodynia observed in a rat nerve injury model. In an effort to determine the site of drug action, effects after intravenous, intrathecal, and regional administration were compared.

Methods: Rats underwent ligation of the left fifth and sixth lumbar spinal nerves. The 50% thresholds (g) for left hind paw withdrawal of awake rats to von Frey hairs were documented before, during, and after intravenous administration of lidocaine at programmed/documented pseudo-steady-state plasma concentrations, and correlated with measured plasma concentrations. Responses to lidocaine application intrathecally and regionally to the injured nerves were also recorded.

Results: In rats with tactile allodynia, intravenous lidocaine yielded 66 +/- 11% of the maximal possible effect on thresholds (100% = normal threshold), versus -1.3 +/- 2.7% for saline infusion. Twenty-one days after lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold increases depended on plasma concentration, rather than quantity of drug administered: rats receiving 15 mg/kg with higher plasma concentrations (1.2 +/- 0.1 micrograms/ml) showed significant allodynia suppression throughout 7 days of follow-up, whereas rats receiving 15 mg/kg at a slower rate with lower plasma concentrations (0.6 +/- 0.1 microgram/ml) did not. The EC50 for acute allodynia suppression was 0.75 microgram/ml. No such allodynia suppression was seen after intrathecal or regional administration of lidocaine despite transient neural blockade.

Conclusions: Intravenous, but not intrathecal or regionally applied, lidocaine produces dose-dependent suppression of allodynia associated with nerve injury. The effects far outlast plasma concentrations of lidocaine. The mechanism of these prolonged effects is unknown.

Publication types

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

MeSH terms

  • Anesthetics, Local / therapeutic use*
  • Animals
  • Dose-Response Relationship, Drug
  • Injections, Intravenous
  • Lidocaine / administration & dosage
  • Lidocaine / blood
  • Lidocaine / therapeutic use*
  • Male
  • Neurons / drug effects
  • Pain / drug therapy*
  • Peripheral Nervous System Diseases / drug therapy*
  • Rats
  • Rats, Sprague-Dawley


  • Anesthetics, Local
  • Lidocaine