ABSTRACT
Title
Metabotropic glutamate receptor subtype 8 in the amygdala: a novel target for inflammatory pain relief
Authors
S. Boccella, E. Palazzo, I. Marabese, L. Luongo, C. Giordano, V. de Novellis, F. Rossi, S. Maione.
Department of Experimental Medicine, Pharmacology Division, The Second University of Naples
Email: enza.palazzo@unina2.it
Department of Experimental Medicine, Pharmacology Division, The Second University of Naples
Email: enza.palazzo@unina2.it
Abstract
The amygdala is a crucial area controlling pain and its emotional component. The role of mGlu8 receptor (mGluR8) in the central nucleus of the amygdala (CeA) on thermoceptive threshold and on CeA serotonin (5-HT), glutamate (Glu) and gamma-aminobutyric acid (GABA) release has been investigated 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-DCPG, a selective mGluR8 agonist, administered into the CeA, did not change 5-HT, Glu and GABA release, 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, 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 (VGAT) positive profiles, has been found in the CeA after carrageenan-induced inflammatory pain. These results show that stimulation of mGluR8, which was over-expressed within the CeA in inflammatory pain conditions, inhibits nociceptive behaviour. 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.