mGluR activation reveals a tonic NMDA component in inflammatory hyperalgesia.
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.
Boxall
S J
SJ
Department of Pharmacology, Novartis Institute for Medical Sciences, London, UK.
Berthele
A
A
Tölle
T R
TR
Zieglgänsberger
W
W
Urban
L
L
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*
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