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 present study, we have examined whether activation of different glutamate receptor subtypes modulates the release of substance P evoked by the C-fiber selective stimulant capsaicin (1 microM) from rat trigeminal nucleus slices. The selective NMDA glutamate receptor agonist L-CCG-IV (1-10 microM) enhanced capsaicin-evoked substance P release about 100%. This facilitatory effect was blocked by 0.3 microM MK-801, a selective NMDA receptor antagonist. The metabotropic glutamate receptor agonists L-AP4 (group III) and DHPG (group I) (30-100 microM) inhibited capsaicin-evoked substance P release by approximately 60%. These inhibitory effects were blocked by the selective metabotropic glutamate receptor antagonist (+/-)-MCPG (5 microM). On the other hand, AMPA and kainate (0.1-10 microM), 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 antagonistic control of some metabotropic and ionotropic glutamate receptor subtypes.
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Related Subject Headings
- alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
- Trigeminal Nuclei
- Substance P
- Receptors, N-Methyl-D-Aspartate
- Receptors, Metabotropic Glutamate
- Receptors, Glutamate
- Rats, Sprague-Dawley
- Rats
- Propionates
- Nociceptors
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
- Trigeminal Nuclei
- Substance P
- Receptors, N-Methyl-D-Aspartate
- Receptors, Metabotropic Glutamate
- Receptors, Glutamate
- Rats, Sprague-Dawley
- Rats
- Propionates
- Nociceptors