Differential effects of NMDA and AMPA/KA receptor antagonists on c-Fos or Zif/268 expression in the rat spinal dorsal horn induced by noxious thermal or mechanical stimulation, or formalin injection.
The involvement of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate (KA) receptors in the induction of c-Fos and Zif/268 expression in spinal dorsal horn neurons following noxious thermal or mechanical stimulation, or formalin injection into the rat hind paw was examined by intrathecal administration of a competitive NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV) or an AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or both, 30 min prior to noxious stimulation. APV caused a significant reduction in the level of c-Fos expression in the superficial layer induced by each of these three noxious stimuli. The effects of APV on Zif/268 expression or of CNQX on c-Fos or Zif/268 expression in the superficial layer induced by these three noxious stimuli were dependent on the type of stimulus applied to the rat hind paw. The noxious thermal stimulus-evoked c-Fos expression level was reduced by APV and/or CNQX, while Zif/268 expression was hardly changed. Both c-Fos and Zif/268 expressions following formalin injection were reduced by APV alone and APV+CNQX, but not by CNQX alone. Zif/268 expression following noxious mechanical stimulation was significantly reduced only by APV+CNQX although APV or CNQX alone did not affect the expression, while c-Fos expression was reduced by APV and APV+CNQX but not by CNQX alone. These findings suggest that NMDA and AMPA/KA receptors are differentially involved in c-Fos and Zif/268 expression in the spinal dorsal horn following noxious thermal, formalin and mechanical stimulation.
Department of Oral and Maxillofacial Surgery, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan.
Omar I F
OI
Rahman
Ryuji
R
Terayama
Tetsuya
T
Ikeda
Mikako
M
Koganemaru
Tadashi
T
Nakamura
Ryosuke
R
Shiba
Toshikazu
T
Nishimori
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005557:Formaldehyde / Q000008:administration & dosage / Q000494:pharmacology; D006358:Hot Temperature; D017874:Immediate-Early Proteins; D007267:Injections; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D010812:Physical Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists; D005557:Formaldehyde; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C486110:Egr1 protein, rat