Effects Of MrgC Receptors On Glia Activation In The Spinal Dorsal Horn Following Chronic Nerve Injury

Mrg (Mas-related gene)receptors are G protein coupled receptors. The majority of its members are exclusively expressed in small neurons of dorsal root ganglia (DRG) and trigeminal ganglia, suggesting that the physiological function of Mrg receptors is related to pain modulation. It has been observed that intrathecal injection of the Mrg C receptor agonist bovine adrenal medulla hormone8-22(BAM8-22) can relieve pain induced by spinal nerve ligation (SNL).This study investigated the possible mechanisms underlying the modulation effect MrgC receptors on neuropathic pain induced by L5spinal nerve ligation. The techniques of behavioral test and immunohistochemical fluorescence staining were used to study:(1) the effect of intrathecal injectin of BAM8-22on mechanical allodynia on the second day following SNL;(2) the effect of intrathecal BAM8-22on microglia expression in the spinal dorsal horn on the second day after surgery;(3) the possible mechanisms involved in the pain modulation by MrgC receptors. The present study demonstrated that intrathecal injection of BAM8-22reduced the mechanical hypersensitivity induced by SNL. Immunofluorescence staining showed that the spinal microglia and nNOS expression in DRG were increased after spinal nerve ligation and injection BAM8-22significantly reversed these alterations. In addition, intrathecal BAM8-22significantly reduced the expression of Toll-like receptor4and metalloproteinases on DRG on the tenth day after ligation.This study showed that intrathecal the MrgC receptor agonist BAM8-22effectively relieved pain caused by chronic nerve injury. This effect may be attributed to the inhibition of the increased expression of spinal microglia and nNOS in DRG Furthermore, the activation of MrgC receptors can also inhibit the established neuropathic pain. The mechanisms involved the suppression of the expression of the proinflammatory cytokines TLR4and MMP2.