AFFERENT C-FIBERS RELEASE SUBSTANCE-P AND GLUTAMATE

Capsaicin is currently used as a specific pharmacological tool for inv estigation of functions of primary afferent C-fibres. Their peripheral terminals play an important role in ''neurogenic inflammation'' media ted by released substance P and calcitonin gene related peptide, where as in the mediation of central functions, activation of the N-methyl-D -aspartate (NMDA) receptors has recently been demonstrated. A method f or continuous monitoring of glutamate concentration was used to study mechanisms of capsaicin-induced glutamate release from rat spinal cord slices. Both capsaicin and substance P released glutamate from spinal dorsal horns in a concentration-dependent manner (EC50 = 0.53 +/- 0.0 7 and 0.37 +/- 0.06 mu M, respectively). The NMDA antagonist MK-801 (1 0 mu M) had no effect on evoked glutamate release, whereas the tachyki nin (NK-1) antagonist CP-99994 (10 mu M) reduced responses to both sti muli (p < 0.001). In capsaicin-desensitized rats, evoked glutamate rel ease from dorsal hems was significantly decreased yet not completely a bolished. Although the evoked glutamate release from ventral horns was markedly smaller than that from dorsal horns, the normalized response s to capsaicin and to substance P were similar. This might be explaine d by smaller amounts of mobilizable glutamate in ventral hems. Our fin dings confirmed the ability of capsaicin to release glutamate mainly f rom the afferent C-fibres in the spinal cord. The observed effect of e xogenous substance P and inhibitory action of the NK-1 antagonist indi cate facilitation of capsaicin-induced glutamate release by coreleased substance P.