Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis

1 We examined the effects of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxali ne-2,3-dione (CNQX) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quino xaline-7-sulphonamide (NBQX), the kainate receptor antagonists gamma-(R-)-g lutamylaminomethanesulphonic acid (GAMS) and 6,7,8,9-tetrahydro-5-nitro-1H- benz[g]indole-2,3-dione-3-oxime (NS-102), and the group III metabotropic gl utamate receptor (mGluR) agonist 2-amino-4-phosphono-S-butanoic acid (L-AP4 ) on c-fos-like immunoreactivity (c-fos LI) in trigeminal caudalis (Sp5C), lateral reticular (LRt), medullary reticular (Md) and solitary tract (Sol) nuclei, after intracisternal injection of capsaicin in urethane anaesthetiz ed Sprague-Dawley rats. 2 Few c-fos labelled cells were observed within Sp5C in capsaicin-vehicle t reated animals. The number of positive c-fos cells increased by 17 fold aft er intracisternal capsaicin (5 nmol) administration. 3 Pretreatment with CNQX (0.02, 0.1, 0.6, 3 and 15 mg kg(-1)) or NBQX (0.01 , 0.1 and 1 mg kg(-1)), administered intraperitoneally 15 min before capsai cin, significantly reduced labelled cells within Sp5C by a maximum of 45 an d 34%, respectively. The number of c-fos LI cells within LRt, Md and Sol wa s not affected. Pretreatment with L-AP4 (1, 3 and 10 mg kg(-1)) decreased t he number of Sp5C c-fos LI cells by a maximum of 30%, whereas GAMS (1 and 1 0 mg kg(-1)) and NS-102 (1 and 5 mg kg(-1)) did not show any significant ef fect. 4 These results suggest that blockade of AMPA receptors, but not kainate re ceptors, or the activation of group III mGluRs, decrease the response of Sp 5C neurons to trigeminovascular activation. Thus, in addition to NMDA recep tors, mGluRs and AMPA receptors may modulate cephalic pain and may provide a potential therapeutic target for antimigraine drugs.