title: mGluR activation reveals a tonic NMDA component in inflammatory hyperalgesia.
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 microM and 51.0 +/- 5.76 microM, 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.
authors.affiliation: Department of Pharmacology, Novartis Institute for Medical Sciences, London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Boxall
authors.forename: A
authors.initials: A
authors.lastname: Berthele
authors.forename: T R
authors.initials: TR
authors.lastname: Tölle
authors.forename: W
authors.initials: W
authors.lastname: Zieglgänsberger
authors.forename: L
authors.initials: L
authors.lastname: Urban
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D007249:Inflammation / Q000139:chemically induced*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D015763:2-Amino-5-phosphonovalerate