抄録
The glutamate receptors in the nervous system are related to nociceptive response. These receptors include the AMPA (α -amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor and the NMDA (N-methyl-D-aspartate) receptor. The purpose of this study was to investigate whether novel antagonists of these glutamate receptors could inhibit the nociceptive response in the spinal cord of male Wistar rats. Rats intrathecally (i.t.) received 0.1 to 10 pmol of Ly-2935582 (a novel AMPA antagonist) and 10 to 1000 pmol of Ly-233053 (a novel NMDA antagonist) dissolved in 50 μl of physiological saline. A 50-μl volume of 2.0% formalin solution was injected as a noxious stimulus into the hindpaw 15 min after the i.t. injections. We measured the total time the animal spent licking the hindpaw in the first 5 min (early phase) and from 10 to 30 min (late phase) after formalin injection. Controlled total licking time was 103±13 sec (mean ± SE) (early phase) and 151±86 sec (late. phase) . The licking time during the early phase was significantly and dose-dependently decreased with intrathecal administrations of both Ly-293558 and Ly-233053 (p<0.05) . However, Ly-293558 induced this effect at much lower concentra-tions. During the late phase, only the highest dose of each antagonist significantly shortened licking time. Our results indicate that these two novel AMPA and NMDA receptor antagonists when intrathecally administrated could induce antinociceptive effects during both the acute phase (peripheral sensitization) and late phase (central sensitization) of formalin-induced nociceptive stimulation without producing motor dysfunction.
