title: Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception.
abstract: The role played 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 pain. 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, respectively, decreased the nociceptive response (-92+/-6% and -89+/-8%, respectively) 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-EGlu (30 nmol/mouse). CPCCOEt is a selective antagonist of group I mGlu receptors, while (2S)-alpha-EGlu is an antagonist of group II. Intra-PAG microinjections of L-SOP (60 and 120 nmol/mouse), a selective agonist of group III mGluRs, induced an increase of the nociceptive response (+95+/-7%) during the late hyperalgesic phase. (R,S)-alpha-M-SOP (70 nmol/mouse), a selective antagonist of group III mGluRs, completely antagonized the L-SOP-induced effect. These results show that PAG mGluRs participate in modulating the late hyperalgesic behaviours induced by formalin. It seems, therefore, possible that group I and group II mGluRs positively modulate PAG antinociceptive descending pathway following a persistent noxious stimulation, while group III mGluRs modulate it negatively.
authors.affiliation: Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, The Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Maione
authors.forename: P
authors.initials: P
authors.lastname: Oliva
authors.forename: I
authors.initials: I
authors.lastname: Marabese
authors.forename: E
authors.initials: E
authors.lastname: Palazzo
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: L
authors.initials: L
authors.lastname: Berrino
authors.forename: A
authors.initials: A
authors.lastname: Filippelli
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005557:Formaldehyde; D008297:Male; D051379:Mice; D008845:Microinjections; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000503:physiopathology*; D014677:Pharmaceutical Vehicles; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D014677:Pharmaceutical Vehicles; D018094:Receptors, Metabotropic Glutamate; D005557:Formaldehyde