RT Journal Article
SR Electronic
T1 Activation of Mas oncogene-related G-protein-coupled (Mrg) receptors inhibits neurochemical alterations in spinal dorsal horn and dorsal root ganglia associated with inflammatory pain in rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.115.225672
DO 10.1124/jpet.115.225672
A1 Dongmei Wang
A1 Peizhong Wang
A1 Jianping Jiang
A1 Qingqin Lv
A1 Xueai Zeng
A1 Yanguo Hong
YR 2015
UL http://jpet.aspetjournals.org/content/early/2015/07/08/jpet.115.225672.abstract
AB Mas oncogene-related G-protein-coupled receptor C (MrgC) is unequally expressed in primary sensory ganglia and has been shown to modulate pathological pain. This study determined the mechanism underlying effect of MrgC receptors on inflammatory pain. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22, 30 nmol) inhibited CFA-evoked hyperalgesia. This was accompanied by the inhibition of protein kinase C-gamma (PKCγ) and phosphorylated extracellular signal-regulated protein kinase (pERK) in the spinal cord and/or dorsal root ganglia (DRG). The CFA injection in the hindpaw induced an increase in Gq, but not Gi and Gs, protein in the spinal dorsal horn. This increase was inhibited by the i.t. administration of BAM8-22. The exposure of DRG cultures to bradykinin (BK, 10 μM) and prostaglandin E2 (PGE2, 1 μM) increased the expression of CGRP and nNOS in small- and medium-sized neurons as well as the levels of CGRP, aspartate and glutamate in the cultured medium. The BK/PGE2-induced alterations were absent in the presence of BAM8-22 (10 nM). These results suggest that the activation of MrgC receptors can modulate the increase in the expression of CGRP and nNOS as well as the release of CGRP and excitatory amino acids in DRG associated with inflammatory pain. This modulation may result in the inhibition of peripheral and central sensitization via suppressing the expression of Gq protein and PKCγ and ERK signaling pathways in the spinal cord and/or DRG. The present study suggests that MrgC receptors may be a novel target for relieving inflammatory pain.