Journal
BRAIN RESEARCH
Volume 973, Issue 2, Pages 252-264Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(03)02525-3
Keywords
mechanical hyperalgesia; heat hyperalgesia; nociception; inflammation; excitatory amino acid
Categories
Funding
- NIDA NIH HHS [DA 11471] Funding Source: Medline
- NIDCR NIH HHS [DE 09737] Funding Source: Medline
- NINDS NIH HHS [NS 25827] Funding Source: Medline
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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 mug/5 mul), but not intraplantar (10 or 100 mug/50 mul), injection of SYM 2081 attenuated the development of capsaicin-evoked heat hyperalgesia suggesting that SYM 2081's antiltyperalgesic effects were due to its central effects. Furthermore, SYM 2081 completely reversed ongoing carrageenan-evoked mechanical hyperalgesia and partially (similar to50%) 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. (C) 2063 Elsevier Science B.V. All rights reserved.
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