Dual modulation effects of Mas-related gene (Mrg) receptors on pain sensitivity in rats

Mas-related gene G protein-coupled (Mrg) receptors have been identified to be uniquely distributed in subpopulations of small-diameter neurons in dorsal root and trigeminal ganglia in rodents and humans. It has been demonstrated that the activation of MrgC receptors in rodents inhibits pathological pain but does not alter pain sensitivity under normal conditions. . In vitro studies have suggested that the activation of MrgX1 or MrgD receptors is associated with dual G proteins. The current study was designed to determine whether rat MrgC receptors are coupled to Gi/o and Gq proteins and what pain behavior response activation of these proteins could mediate. Intrathecal (i.t.) administration of bovine adrenal medulla 8-22 (BAM8-22), a specific MrgC receptor agonist, dose-dependently decreased tail flick latency (TFL) in rats pretreated with pertussis toxin, but not with saline. On the other hand, i.t. injected BAM8-22 increased TFL in the presence of U73122 but produced no changes in TFL following pretreatment with saline. The results in the present study provide . in vivo evidence that both Gi/o and Gq proteins are involved in MrgC receptor signaling.