Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw.
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 ED(50) values of 2.6 (1.6-4.3) and 0.5 (0.4-0.7) micromol/kg, respectively. Pretreatment with Chicago sky blue 6B (100 microg/kg), an inhibitor of glutamate uptake, caused a significant (about sixfold) reduction of the mean ED(50) 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.
Beirith
Alessandra
A
Department of Pharmacology, Centre of Biological Sciences, Federal University of Santa Catarina, Rua Ferreira Lima, 82, Florianópolis, SC, 88015-420, Brazil.
Santos
Adair R S
AR
Calixto
João B
JB
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005121:Extremities; D018698:Glutamic Acid / Q000494:pharmacology*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014343:Trypan Blue
D001391:Azo Compounds; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D020030:Nitric Oxide Donors; D009573:Nitrites; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D005973:Glutamine; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D019335:Nitroarginine; C009000:pontamine sky blue; D009569:Nitric Oxide; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C042626:gamma-glutamylaminomethylsulfonic acid; D010396:Penicillamine; D014343:Trypan Blue