title: Metabotropic glutamate receptor subtype 8 in the amygdala modulates thermal threshold, neurotransmitter release, and rostral ventromedial medulla cell activity in inflammatory pain.
abstract: The amygdala is a crucial area in controlling the threshold of pain and its emotional component. The present study has evaluated the effect of a metabotropic glutamate 8 receptor (mGluR8) stimulation in the central nucleus of the amygdala (CeA) on the thermoceptive threshold and on CeA serotonin (5-HT), glutamate (Glu), and GABA release in normal and carrageenan-induced inflammatory pain conditions in rats. Furthermore, the activity of rostral ventromedial medulla (RVM) putative "pronociceptive" ON and "antinociceptive" OFF cells has been evaluated. (S)-3,4-Dicarboxyphenylglycine [(S)-3,4-DCPG], a selective mGluR8 agonist, administered into the CeA, did not change 5-HT, Glu, and GABA release, or the thermoceptive threshold, nor did it modify the activity of ON and OFF cells of the RVM in normal animals. In rats treated with carrageenan, intra-CeA (S)-3,4-DCPG perfusion produced antinociception, and increased 5-HT and Glu, whereas it decreased GABA release. Intra-CeA (S)-3,4-DCPG inhibited ON and increased OFF cell activities. Furthermore, an increase in mGluR8 gene, protein, and staining, the latter being associated with vesicular GABA transporter-positive profiles, has been found in the CeA after carrageenan-induced inflammatory pain. These results show that stimulation of mGluR8, which was overexpressed within the CeA in inflammatory pain conditions, inhibits nociceptive behavior. Such an effect is associated with an increase in 5-HT and Glu release, a decrease in GABA, and the inhibition of ON- and the stimulation of OFF-cell activities within RVM.
authors: Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, The Second University of Naples, 80138 Naples, Italy. enza.palazzo@unina2.it
authors: Enza
authors: E
authors: Palazzo
authors: Ida
authors: I
authors: Marabese
authors: Marie
authors: M
authors: Soukupova
authors: Livio
authors: L
authors: Luongo
authors: Serena
authors: S
authors: Boccella
authors: Catia
authors: C
authors: Giordano
authors: Vito
authors: V
authors: de Novellis
authors: Francesca
authors: F
authors: Rossi
authors: Sabatino
authors: S
authors: Maione
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology; D015153:Blotting, Western; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D017551:Microdialysis; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012684:Sensory Thresholds / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013697:Thermosensing / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C110733:3,4-dicarboxyphenylglycine; D000596:Amino Acids; D001565:Benzoates; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D002351:Carrageenan; D005998:Glycine