Opposite modulation of capsaicin-evoked substance P release by glutamate receptors

Substance P and glutamate are present in primary afferent C-fibers and play important roles in persistent inflammatory and neuropathic pain. In the pr esent study, we have examined whether activation of different glutamate rec eptor subtypes modulates the release of substance P evoked by the C-fiber s elective stimulant capsaicin (1 mu M) from rat trigeminal nucleus slices. T he selective NMDA glutamate receptor agonist L-CCG-IV (1-10 mu M) enhanced capsaicin-evoked substance P release about 100%. This facilitatory effect w as blocked by 0.3 mu M MK-801, a selective NMDA receptor antagonist. The me tabotropic glutamate receptor agonists L-AP4 (group III) and DHPG (group I) (30-100 mu M) inhibited capsaicin-evoked substance P release by approximat ely 60%. These inhibitory effects were blocked by the selective metabotropi c glutamate receptor antagonist (+/-)-MCPG (5 mu M). On the other hand, AMP A and kainate (0.1-10 mu M), did not significantly affect capsaicin-evoked substance P release. Thus, substance P release from non-myelinated primary afferents, and possibly nociception, may be under the functional antagonist ic control of some metabotropic and ionotropic glutamate receptor subtypes. (C) 1999 Elsevier Science Ltd. All rights reserved.