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)