Cellular Mechanisms Underlying The Inhibition Of L5-spinal Nerve Ligation-induced Naueopathic Pain By MrgC Receptors In Rats

Mas-related gene G-protein-coupled receptors (Mrg) are orphan G protein-coupled receptors. It has been found that the receptor gene homology with Masl carcinoma is very high, These receptors are named Mas-related gene G protein-coupled receptors, or Mrg receptors. Its mRNA are expressed uniquely in small-sized neuron in trigeminal ganglia (TG) and dorsal root ganglion (DRG),so it is also called sensory neuron-specific receptor. Study has demonstrated that the MrgC receptor agonist BAM8-22alleviates SNL-induced allodynia in rats. This finding indicates that it is of interest to study physiology and pharmacology of MrgC receptors.This study was aimed to investigate the cellular mechanisms underlying the inhibition of MrgC receptors on SNL-evoked neuropathic pain by using behavioral, immunhstochemical, western blot techniques. We examined the effect of intrathecal administration of the MrgC receptor agonist BAM8-22on mechanical allodynia on the10th day after L5spinal nerve ligation.The results showed:(1) the mechanical pain threshold decreased obviously after L5spinal nerve ligation,(2) the astrocytes were activated evidenced by the increase in GFAP, IL-1β and nNOS proteins expression in the spinal dorsal horn,(3) the CREB and ERK1/2signaling pathways were activated. Interestingly intrathecal injection of BAM8-22inhibited all these alterations. Thefore, these results provided evidence showing that:activating MrgC receptors can inhibit nerve injury-induced activation and functions of astrocytes.The present study suggests that activation of MrgC receptors can alleviate the nerve injury-induced pain hypersensitivity.The mechanisms underlying this effect include the inhibition of astrocyte activation, synthesis of IL-1β and nNOS as well as of CREB and ERK1/2signaling pathways.