Involvement of spinal N-methyl-D-aspartate receptors in capsaicin-induced in vivo release of substance P in the rat dorsal horn.

The aim of the present in vivo microdialysis study was to determine the possible contribution of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate (KA) receptors to capsaicin-induced release of substance P-like immunoreactivity (SP-LI) in the dorsal horn of the rat. Perfusion of a microdialysis probe with capsaicin (50 or 100 microM) induced a significant eight-fold increase of the extracellular SP-LI level. The capsaicin (50 microM)-evoked release of SP-LI was blocked by spinal administration of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (D-APV; 5 mM), but not by the AMPA/KA antagonist 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione disodium (NBQX; 0.5 mM). In contrast, the SP-LI release induced by 100 microM capsaicin could not be prevented by D-APV (10 mM) or NBQX (0.5 mM). The data suggest that the spinal SP-LI release induced by a moderate concentration of capsaicin is in part dependent on the release of glutamate acting on NMDA receptors.