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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Anesthesiology, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan, maedamih@is.icc.u-tokai.ac.jp.
Miho
M
Ito
Masanobu
M
Yoshikawa
Kenji
K
Ito
Mitsumasa
M
Matsuda
Xing Lu
XL
Jin
Shigeru
S
Takahashi
Hiroyuki
H
Kobayashi
Toshiyasu
T
Suzuki
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D005557:Formaldehyde; D057967:Infusions, Intraventricular; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D015363:Quinolones / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D012694:Serine / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D015363:Quinolones; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D012694:Serine; C094635:L 701324