mGluR activation reveals a tonic NMDA component in inflammatory hyperalgesia

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Abstract
METABOTROPIC glutamate receptors (mGluRs) have been shown to contribute to nociceptive processing in the spinal cord. We have investigated the pharmacology of the mGluR agonist (1S,3R)-ACPD during inflammatory hyperalgesia in an in vitro preparation of the juvenile rat hemisected spinal cord. Superfusion of (1S,3R)-ACPD produced a concentration-dependent ventral root depolarization in naive and hyperalgesic animals with no significant difference in EC50 values (55.5 ± 6.36 μM and 51.0 ± 5.76 μM, respectively, n = 4). However, the amplitude of the maximum response was significantly enhanced by 23% in hyperalgesic compared with naive animals. The NMDA receptor antagonist D-AP5 reversed this effect, leaving the (1S,3R)-ACPD dose-response curve unchanged in naive animals. These results suggest a tonic NMDA component in the spinal cord during inflammatory hyperalgesia.