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Journal of Neuroscience, Vol 12, 3665-3670, Copyright © 1992 by Society for Neuroscience
The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury
TJ Coderre and R Melzack
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
The contribution of excitatory amino acids (EAAs) to the development of
central sensitization and persistent nociception in response to tissue
injury in rats was examined following the subcutaneous injection of
formalin into the hindpaw. Formalin-induced nociceptive behaviors were
enhanced by intrathecal pretreatment with the EAAs L-glutamate and L-
aspartate. An enhancement of the formalin nociceptive response was also
produced by intrathecal pretreatment with the receptor-selective EAA
agonists NMDA and trans-(+/- )-1-amino-1,3-cyclopentane dicarboxylic acid
(ACPD), but not (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4- propionic
acid hydrobromide (AMPA). The effect of NMDA was enhanced by a combined
administration with AMPA or APCD. Formalin nociceptive responses were
dose-dependently reduced by intrathecal pretreatment with the NMDA receptor
antagonists 2-amino-5-phosphonovaleric acid (APV) and (+)-MK-801 hydrogen
maleate, but not the selective AMPA antagonist
6-cyano-7-nitroquinoxaline-2,3-dione or the selective metabotropic EAA
receptor antagonist 2-amino-3-phosphonopropionic acid. The results suggest
that EAAs acting at the NMDA receptor contribute to central sensitization
and persistent nociception following subcutaneous formalin injection.
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