Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception. 2000

S Maione, and P Oliva, and I Marabese, and E Palazzo, and F Rossi, and L Berrino, and A Filippelli
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, The Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D010146 Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D010487 Periaqueductal Gray Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain. Mesencephalic Central Gray,Midbrain Central Gray,Central Gray Substance of Midbrain,Central Periaqueductal Gray,Griseum Centrale,Griseum Centrale Mesencephali,Periaqueductal Gray Matter,Substantia Grisea Centralis,Substantia Grisea Centralis Mesencephali,Central Gray, Mesencephalic,Central Gray, Midbrain,Gray Matter, Periaqueductal,Gray, Central Periaqueductal,Griseum Centrale Mesencephalus,Periaqueductal Grays, Central
D005557 Formaldehyde A highly reactive aldehyde gas formed by oxidation or incomplete combustion of hydrocarbons. In solution, it has a wide range of uses: in the manufacture of resins and textiles, as a disinfectant, and as a laboratory fixative or preservative. Formaldehyde solution (formalin) is considered a hazardous compound, and its vapor toxic. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p717) Formalin,Formol,Methanal,Oxomethane
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D014677 Pharmaceutical Vehicles A carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. (Dictionary of Pharmacy, 1986) Pharmaceutical Vehicle,Vehicle, Pharmaceutical,Vehicles, Pharmaceutical
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018094 Receptors, Metabotropic Glutamate Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action. Glutamate Receptors, Metabotropic,Metabotropic Glutamate Receptors,Receptors, Glutamate, Metabotropic,Metabotropic Glutamate Receptor,Glutamate Receptor, Metabotropic,Receptor, Metabotropic Glutamate

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