Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception

The role prayed by periaqueductal gray (PAG) matter metabotropic glutamate receptors (mGluRs) in the modulation of persistent noxious stimulation was investigated in mice. The formalin test was used as a model of persistent p ain. Intra-PAG microinjections of(S)-3,5-DHPG (25 and 50 nmol/mouse) and L- CCG-I (30 and 60 nmol/mouse), agonists of group I and group II mGluRs, resp ectively, decreased the nociceptive response (-92 +/- 6% and -89 +/- 8%, re spectively) during the late phase. No change of the early nociceptive phase was observed after (S)-3,5-DHPG or L-CCG-I treatments. These effects were antagonized by a pretreatment with CPCCOEt (40 nmol/mouse) and (2S)-alpha-E Glu (30 nmol/mouse). CPCCOEt is a selective antagonist of group I mGlu rece ptors, while (2S)-alpha-EGlu is an antagonist of group IT. Intra-PAG microi njections of L-SOP (60 and 120 nmol/mouse), a selective agonist of group II I mGluRs, induced an increase of the nociceptive response (+95 +/- 7%) duri ng the late hyperalgesic phase. (R,S)-alpha-M-SOP (70 nmol/mouse), a select ive antagonist of group III mGluRs, completely antagonized the L-SOP-induce d effect. These results show that PAG mGluRs participate in modulating the late hyperalgesic behaviours induced by formalin. It seems, therefore, poss ible that group I and group II mGluRs positively modulate PAG antinocicepti ve descending pathway following a persistent noxious stimulation, while gro up III mGluRs modulate it negatively. (C) 2000 International Association fo r the Study of Pain. Published by Elsevier Science B.V. All rights reserved .