Excitatory amino acids acting at non-
NMDA receptors contribute to transmission of nociceptive information.
SYM 2081 ((2S,4R)-4-methyl glutamic acid) desensitizes
kainate receptors, one subtype of non-
NMDA receptors, to subsequent release of
excitatory amino acids and thus may attenuate transmission of nociceptive information. To determine if
SYM 2081 can prevent development of
hyperalgesia,
SYM 2081 (10, 50 or 100 mg/kg, i.p.) was administered prior to injection of
capsaicin into the hindpaw of rats, which produces mechanical and heat
hyperalgesia. To determine if
SYM 2081 can reduce ongoing inflammatory
hyperalgesia,
SYM 2081 (10 or 100 mg/kg, i.p.) was administered after development of
carrageenan-evoked
hyperalgesia. Intraplantar injection of
capsaicin produced an increase in hindpaw withdrawal frequency to mechanical stimuli (from 4+/-2 to 41+/-7%; mean+/-S.E.M.) and a decrease in withdrawal latency to heat (from 12.3+/-0.3 to 5.9+/-0.4 s) in rats that received vehicle. In contrast, rats that received
SYM 2081 (100 mg/kg) prior to injection of
capsaicin exhibited a lower hindpaw withdrawal frequency (18+/-4%) and a longer withdrawal latency (7.7+/-0.5 s). Intrathecal (1-100 microg/5 microl), but not intraplantar (10 or 100 microg/50 microl), injection of
SYM 2081 attenuated the development of
capsaicin-evoked heat
hyperalgesia suggesting that
SYM 2081's antihyperalgesic effects were due to its central effects. Furthermore,
SYM 2081 completely reversed ongoing
carrageenan-evoked
mechanical hyperalgesia and partially (approximately 50%) reversed ongoing heat
hyperalgesia. The present study demonstrates that administration of a high-potency
ligand that selectively desensitizes
kainate receptors attenuates the development of mechanical and heat
hyperalgesia and attenuates ongoing inflammatory
hyperalgesia.