Intrathecal N-methyl-d-aspartate (NMDA) activates both nociceptive and antinociceptive systems

Gladys Raigorodsky, Gideon Urca*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Injection of the excitatory amino acid N-methyl-d-aspartate (NMDA) into the spinal subarachnoid space of rats produces both hyperalgesic and analgesic effects. At lower concentrations (0.5 mM) little behavioral effect is elicited by the drug. However, brief hyperalgesia followed by several minutes of analgesia can be detected in these animals. Higher concentrations of the drug produce vocalization, caudally directed scratching and biting and hyper-responsiveness to light touch. The NMDA antagonist, arginine vasopressin, produces analgesia when injected by itself and completely reverses all effects of NMDA. NMDA-induced analgesia, but not hyperalgesia, is reversed by intrathecal administration of naloxone, methylsergide and phentolamine. The analgesic effects of both agonist and antagonist are markedly potentiated by spinalization. These results suggest the involvement of NMDA receptors in both the transmission of pain and the mediation of spinal segmental pain inhibitory mechanisms.

Original languageEnglish
Pages (from-to)158-162
Number of pages5
JournalBrain Research
Issue number1
StatePublished - 29 Sep 1987


  • Analgesia
  • Excitatory amino acid
  • N-Methyl-d-aspartate
  • Pain
  • Spinal cord


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