Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study

Anesth Analg. 1999 Oct;89(4):985-8. doi: 10.1097/00000539-199910000-00030.


Neuropathic pain responds inconsistently to opioids and nonsteroidal antiinflammatory drugs. However, oral anticonvulsants have a proven analgesic effect on neuropathic pain, but may not be practical in an acute flare-up. Phenytoin was the first oral anticonvulsant used as an analgesic for neuropathic pain. There have been few studies on the parenteral analgesic effect of this drug. In this randomized, double-blind, placebo-controlled, crossover study of 20 patients with acute flare-ups of neuropathic pain, we compared a 2-h placebo infusion with a 2-h infusion of 15 mg/kg phenytoin. Overall pain, shooting pain, burning pain, paresthesia, numbness, and sensitivity were measured using a 10-cm linear visual analog score. Numbness and sensitivity were reduced in the placebo group during infusion, but not in the 7 days after infusion. In the phenytoin group, there were significant reductions in burning pain (P < 0.05), shooting pain (P < 0.001), sensitivity (P < 0.001), numbness (P < 0.05), and overall pain (P < 0.005) during the infusion period. The reduction in overall pain persisted for 1 day, in sensitivity for 2 days, and in shooting pain for 4 days after infusion. We conclude that IV infusion of 15 mg/kg phenytoin has an analgesic effect in acute flare-ups of neuropathic pain and that this relief outlives both the infusion time and plasma half-life of phenytoin.

Implications: Oral phenytoin can relieve neuropathic pain. The aim of this study was to examine the effect of IV phenytoin on neuropathic pain. The results indicate that IV phenytoin may be used to treat flare-ups of chronic neuropathic pain.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Analgesics / blood
  • Analgesics / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Neuralgia / physiopathology
  • Pain Measurement
  • Paresthesia / drug therapy
  • Paresthesia / physiopathology
  • Phenytoin / administration & dosage
  • Phenytoin / blood
  • Phenytoin / therapeutic use*
  • Placebos
  • Recurrence
  • Sensation / drug effects
  • Sensation Disorders / drug therapy
  • Sensation Disorders / physiopathology


  • Analgesics
  • Placebos
  • Phenytoin