The Role of Peripheral N-Methyl-D-Aspartate (NMDA) Receptors in Freund's Complete Adjuvant Induced Mechanical Hyperalgesia in Rats / 대한마취과학회지

ABSTRACT

BACKGROUND: While the effects of excitatory amino acids have been characterized in the central nervous system, relatively little is known about their possible modulation of elements responsible for hyperalgesia within peripheral tissue. The purpose of this study was to investigate the role of excitatory amino acid receptors in mechanical hyperalgesia induced by a subcutaneous injection of Freund's complete adjuvant (FCA) into the rat hind paw. METHODS: Inflammations were induced by injecting FCA on the dorsal surface of the right hind paw of rats. Effects of excitatory aminoacid agonists or antagonists on mechanical hyperalgesia were investigated by a subcutaneous injection of a drug to the inflamed paw. Mechanical hyperalgesia was expressed as percent change in paw withdrawal threshold compared to baseline value that was measured before drug injection after inflammation was induced with FCA. RESULTS: In normal rats, an intraplantar (i.pl.) injection of L-glutamate, but not of D-glutamate (3 pmol/0.1 ml each) produced a mechanical hyperalgesia in the hind paw with a lowered paw paw-withdrawal threshold to pressure. In rats that developed the mechanical hyperalgesia associated with inflammation in the hind paw following an i.pl. injection of FCA (0.15 ml), the injection of a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (1 pmol/0.1 ml) into the inflamed paw increased the paw pressure threshold (24.24.6% increase from baseline, P < 0.05). On the other hand, the injection of a non-NMDA receptor antagonist, 6-cyano-7-nitroqiunoxaline-2,3-dione (CNQX, 10 pmol/0.1 ml) into the inflamed paw had no effect on the FCA-induced lowering of the paw pressure threshold. CONCLUSIONS: The results suggest that NMDA, but not non-NMDA receptors play a substantial role in mediating the development of mechanical hyperalgesia induced in the inflamed paw following an i.pl. FCA injection.