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This study characterizes the receptor subtypes and investigates some of the mechanisms by which glutamate, injected intraplantarly (i.pl.) into the mouse paw, produces nociception and paw oedema. I.pl. injection of glutamate induced a rapid-onset, dose-related pain response associated with oedema formation, with mean ED₅₀ values of 2.6 (1.6–4.3) and 0.5 (0.4–0.7) μmol/kg, respectively. Pretreatment with Chicago sky blue 6B (100 μg/kg), an inhibitor of glutamate uptake, caused a significant (about sixfold) reduction of the mean ED₅₀ value for glutamate-induced nociception, but not paw oedema. NMDA receptor antagonist MK 801, given by systemic (i.p.), intracerebroventricular (i.c.v.), i.pl. or intrathecal (i.t.) routes, produced graded inhibition of glutamate-induced nociception. Non-NMDA receptor antagonists NBQX or GAMS, metabotropic antagonist E4CPG, and also the antagonist that acts at the NMDA …