The Effect Of MrgC Receptor On Bone Cancer Pain In Rats And Its Cellular Mechanism

Mrg(Mas-related gene receptors)specifically distributed on the small neurons of the dorsal root ganglion and the trigeminal ganglia,belongs to the G protein coupled receptor family.Melanin hormone(MSH,(Tyr6)-γ2-MSH6-12)is one of the effective agonists of Mrg C receptor.Intrathecal MSH can effectively inhibit hyperalgesia in rats.There is information that the activation of microglia and bone cancer pain,and activated microglia can common modulation of bone cancer pain and inflammatory cytokine of IL-1β and n NOS.Through the experiments of intrathecal injection of MSH agonist Mrg C receptor activation,using behavioral techniques,immunohistochemistry and Western Blot to investigate the modulation effect on a rat model of bone cancer pain:(1)Changes in the behavior of rat tibia after the establishment of cancer pain model;(2)The effects of intrathecal injection of Mrg C receptor agonist MSH on rats’ mechanical allodynia induced by bone cancer pain;(3)The effects intrathecal injection of MSH on the expression of microglia and IL-1β and n NOS in the spinal cord of bone cance rats;(4)The effects of intrathecal injection of MSH on the expression of IL-1β and n NOS in DRG of bone cance rats.The results showed that:(1)The mechanical withdrawal threshold of rat was significantly decreased after establishing model of tibial cancer pain;(2)Intrathecal injection of MSH can significantly improve the rat paw withdrawal mechanical threshold;and in the administration of the first 40-60 min,reached the highest efficacy;(3)Intrathecal injection of MSH can effectively inhibit BCP rats’ microglia expression in their spinal cord;(4)The expression of IL-1β and n NOS protein in spinal cord and DRG in the rat model of bone cancer pain were increased significantly intrathecal injection of MSH significantly reduced the expression of IL-1β and n NOS protein in the spinal cord and DRG in rats,which returned to the normal level.The above results show that intrathecal injection of MSH could activate Mrg C receptor agonist,has anti allodynic effect on a rat model of bone cancer pain,produce a certain analgesic effect.This mechanism may be through inhibiting the expression of IL-1β and n NOS in DRG,to further suppress the expression of microglia and IL-1β 、n NOS in rat spinal cord to reduce the bone cancer pain caused by hypersensitivity phenomenon.