期刊
BRAIN RESEARCH
卷 924, 期 2, 页码 219-228出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(01)03240-1
关键词
mouse; glutamate; nociception; paw edema; nitric oxide; NMDA
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) mumol/kg, respectively. Pretreatment with Chicago sky blue 613 (100 mug/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 receptor-associated glycine binding site felbamate, significantly inhibited the nociception induced by glutamate. L-omega-N-nitro-arginine (given i.p., i.t., i.pl. or i.c.v.) prevented the nociception and paw oedema caused by glutamate, an effect that was reversed by L-arginine but not by D-arginine. S-nitroso-N-acetyl-D,L-penicillamine (SNAP), given i.pl.. greatly potentiated glutamate-induced nociception and oedema formation. Finally, the i.pl, injection of glutamate was accompanied by a graded increase in the nitrite levels of the hindpaw exudate. It is concluded that the nociception caused by i.pl. injection of glutamate probably involves the activation of NMDA and non-NMDA receptors by a mechanism which largely depends on the activation of L-arginine-nitric oxide pathway. Glutamate-induced paw oedema seems to be primarily mediated by non-NMDA ionotropic glutamate receptors and release of nitric oxide. (C) 2002 Elsevier Science B.V. All rights reserved.
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