Differential effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on spinal release of amino acids after development of acute arthritis in rats.
Following induction of acute knee joint arthritis in rats, an increase in the release of amino acids in the spinal dorsal horn occurs in two phases: (1) at the time of injection for all amino acids tested; and (2) a late prolonged phase for aspartate (Asp) and glutamate (Glu) (3.5-8 h). In the present study, the increased late phase release of Glu was reversed by posttreatment of the spinal cord with the N-methyl-D-aspartate (NMDA) receptor antagonist, AP7, but not with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Asp late phase release in arthritic animals was unaffected by posttreatment of the spinal cord with either AP7 or CNQX. Arthritic animals became hyperalgesic to radiant heat stimuli by 4 h and this hyperalgesia was reversed by both CNQX and AP7. During the paw withdrawal latency (PWL) test for heat hyperalgesia, there was an increase in the glycine (Gly) and serine (Ser) concentrations in the dorsal horn. This increase in Gly and Ser was blocked by both CNQX and AP7. Indications of inflammation in arthritic animals posttreated with AP7, including increased joint circumference and temperature, were similar to animals that did not receive antagonists. Arthritic animals posttreated with CNQX, however, showed a reduction in the degree of joint swelling. Thus, both non-NMDA and NMDA receptors appear to play a role in the processing of the information evoked by stimuli in the periphery. The arthritis-induced release of Gly and Ser during the PWL test for heat hyperalgesia appears to be dependent on activation of both non-NMDA and NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Sluka
K A
KA
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-0843.
Jordan
H H
HH
Willis
W D
WD
Westlund
K N
KN
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology*; D000208:Acute Disease; D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism; D007596:Joints / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000378:metabolism*
D000596:Amino Acids; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid