Mas-related gene C(MrgC)receptor activation induced inhibition of neurochemical alterations in the spinal dorsal horn and dorsal root ganglia in a rat model of bone cancer pain
Cancer pain is one of the most common symptoms in patients with advanced cancer.In this study,we aimed to investigate the effects of the Mas-related gene C(MrgC)receptors on bone cancer pain.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured after the inoculation of Walker 256 mammary gland carcinoma cells into the tibia of adult Sprague-Dawley rats.The effects of MrgC receptor agonist bovine adrenal medulla 8-22(BAM8-22)on nociceptive behaviors were investigated after intrathecal injection on days 16 and 17.Glial fibrillary acidic protein(GFAP)-positive cells in the spinal dorsal cord,and calcitonin gene related peptide(CGRP)-,neuronal nitric oxide synthase(nNOS)-and IL-1β-positive neurons in the dorsal root ganglia(DRG)were examined by immunofluorescence staining.The expression of nNOS and IL-1β proteins in the spinal dorsal horn and the DRG was examined by Western blotting after treatment with(Tyr6)-γ2-MSH-6-12(MSH),which was another MrgC receptor agonist.The results showed that intrathecal injection of BAM8-22(30 nmol)attenuated mechanical allodynia in a rat model of bone cancer pain and the effects could last for about 60 min,and single administration of BAM8-22 for two consecutive days reduced mechanical allodynia by about half on the third day.Moreover,the number of GFAP-positive cells in the spinal dorsal horn,and the number of CGRP-,nNOS-and IL-1β-positive neurons in the DRG were decreased.Similarly,intrathecal administration of MSH(15 nmol)reduced the expression of nNOS and IL-1 β in the spinal dorsal horn and the DRG.In conclusion,activation of MrgC receptors suppresses the activation of astrocytes in the spinal dorsal cord and the expression of CGRP,nNOS,and IL-1β in the spinal dorsal cord and/or DRG,which may underlie the inhibition of bone cancer pain.These findings provide a novel strategy for the treatment of bone cancer pain.
Mas-related gene C(MrgC)receptorsallodyniaspinal dorsal horndorsal root ganglion(DRG)neurochemistrybone cancer pain
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