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J Anesth. 2014 Apr;28(2):228-34. doi: 10.1007/s00540-013-1708-3. Epub 2013 Sep 19.

Antinociceptive effect of intracerebroventricular administration of D-serine on formalin-induced pain.

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  • 1Department of Anesthesiology, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan, maedamih@is.icc.u-tokai.ac.jp.



In a previous study using the tail-flick test, we found that intracerebroventricular administration of D-serine, an endogenous co-agonist at the glycine sites of N-methyl-D-aspartate (NMDA) receptors, elicited an antinociceptive effect on thermal nociception. The purpose of the present study was to evaluate the effect of intracerebroventricular administration of D-serine on nociception induced by tissue damage or inflammation using the formalin test.


Infusion of drugs into the third ventricle in rat was performed via indwelling cannulae. Drugs were infused at a volume of 10 μl over 2 min, and the infusion cannula was left in place for 2 min before removal. The formalin test was performed 10 min after drug administration.


Intracerebroventricular administration of D-serine significantly and dose-dependently decreased the number of flinches in both the early and late phases in the formalin test. This antinociceptive effect was antagonized by intracerebroventricular administration of L-701,324, a selective antagonist at the glycine sites of NMDA receptors.


The present data suggest that activation of NMDA receptors via glycine sites at the supraspinal level induces an antinociceptive effect on both acute and tonic pain.

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