Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-over comparison with morphine and placebo

Pain. 1994 Sep;58(3):347-354. doi: 10.1016/0304-3959(94)90129-5.


Pain and sensory thresholds were examined before and after intravenous administration of ketamine (0.15 mg/kg), morphine (0.075 mg/kg) or saline in 8 patients with post-herpetic neuralgia. A randomized, double-blind, cross-over study design was used. Post-herpetic neuralgia was associated with impaired sensory function, as shown by reduced tactile and warm sensation in the affected compared with the contralateral non-affected skin area. Neither ketamine nor morphine changed significantly the thresholds for warm, cold, heat pain or tactile sensation. However, ketamine normalized abnormal heat pain sensations in 4 patients, probably due to a central effect. Ketamine, but not morphine, produced significant relief of pain. Pain evoked by non-noxious stimulation of the skin (allodynia) was significantly inhibited by ketamine as well as by morphine. Wind-up-like pain (i.e., pain evoked by repeatedly pricking the affected skin area) was significantly inhibited by ketamine, but significantly aggravated by morphine. Side effects were observed in all the 8 patients after injection of ketamine and in 6 patients after injection of morphine. The present results support the hypothesis that the N-methyl-D-aspartic acid (NMDA) receptors are involved in the control of post-herpetic neuralgia including allodynia and wind-up-like pain. The NMDA receptors also may play a role in the modulation of thermal perception.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Herpesviridae Infections / physiopathology*
  • Hot Temperature
  • Humans
  • Ketamine / adverse effects
  • Ketamine / therapeutic use*
  • Male
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Neuralgia / drug therapy*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Morphine