The contribution of metabotropic glutamate receptors (mGluRs) to formalin-induced nociception.
The present study examined the role of mGluRs in nociceptive responses of male Long-Evans rats following a subcutaneous (s.c.) injection of 1% (30 microliters) or 2.5% (50 microliters) formalin to the plantar surface of the hindpaw. Intrathecal (i.t.) administration of the mGluR4/mGluR6-mGluR8 agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), the mGluR1/mGluR5 antagonists. (S)-4-carboxyphenylglycine ((S)-4CPG) or (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG), but not the non-selective antagonist, (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG), to the lumbar spinal cord slightly reduced second phase nociceptive responses. An i.t. injection of the mGluR1/mGluR5 agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) or the mGluR2/mGluR3 agonist, (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD), but not (2S,1'R,2'R,3'R)-2-(2'3-dicarboxy-cyclopropyl)-glycine (DCG-IV), dose-dependently enhanced formalin-induced nociception in the second phase. In addition, the facilitation of nociceptive responses induced by (1S,3S)-ACPD or (RS)-DHPG was reduced by prior i.t. administration of the mGluR antagonists, (+)-MCPG or (S)-4C3HPG, respectively, as well as by the N-Methyl-D-aspartate (NMDA) receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5). These results indicate that although mGluRs may play a minor role in formalin-induced nociception, mGluR agonist-related facilitation of formalin scores may reflect an interaction with the NMDA receptor.
Fisher
K
K
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Coderre
T J
TJ
D000613:Aminobutyrates; D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005557:Formaldehyde; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology
D000613:Aminobutyrates; D001565:Benzoates; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C078245:4-carboxy-3-hydroxyphenylglycine; C079694:alpha-methyl-4-carboxyphenylglycine; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005557:Formaldehyde; C079215:3,5-dihydroxyphenylglycine; C079693:4-carboxyphenylglycine; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine