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Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Local Anesthesia/Pain

COMBINATION OF NMDA AND AMPA RECEPTOR ANTAGONISTS, AND ANTINOCICEPTION AT THE SPINAL LEVEL IN RATS

Notsuka, H MD; Hamada, F MD; Benson, KT MD; Totoki, T MD; Goto, H MD

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doi: 10.1097/00000539-199802001-00299
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Abstract S301

Introduction: The AMPA receptor and NMDA receptor are well known as glutamate receptors in the nervous system [1]. In this study we investigated the antinociceptive effects of novel antagonists of these glutamate receptors in rats using a formalin test.

Methods: Male Wistar rats (250-340g) were anesthetized with methyl ether, and the S1 spinous process was removed through a caudal cutaneous vertical incision (1 cm in length). We waited two hours for the rats to acclimate to the study environment and to become fully awake. Lumbar punctures were performed with 27-gauge needles between L6 and S1. Several different single doses of LY293558 (the structurally novel selective, competitive AMPA receptor antagonist; A) and LY233053 (the structurally novel selective, competitive NMDA antagonist; N) and combinations of each single dose with predetermined maximum effective doses of each agent, dissolved in 50[micro sign]l normal saline, were injected intrathecally (i.t.). Formalin 2% solution in a volume of 50[micro sign]l was injected s.c. into the plantar surface of the left hind paw 15 min after the i.t. injections. At 5 min intervals from 10 to 60 min (the late phase) after formalin injections, we measured the total licking time the animal spent licking the hind paw. From the total licking time in the late phase, % maximum possible effect (%MPE) was calculated for quantitative comparison.

Results: Data are shown in Figure 1 and Figure 2.

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Figure 1
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Figure 2

Conclusion: Lower dose of N and the maximum effective dose of A appear to be antagonistic for antinociception (Figure 1). This may suggest that lower doses of N may block an NMDA-mediated inhibitory pathway when AMPA receptors are maximally blocked. Even when NMDA receptors are maximally blocked, %MPEs do not change over a wide range of concentrations of A (Figure 2). Data may suggest that these two receptors appear to work in series and inhibition of one is not independent from inhibition of the other.

REFERENCES

1. Pain 45:309-321, 1990.
© 1998 International Anesthesia Research Society