Intra-periqueductal gray injection of melanocortin-4 receptor antagonist HS014 inhibits bone cancer pain in rats

Objective To investigate the effects of melanocortin-4 receptor antagonist HS014 on astrocyte activation of spinal cord in bone cancer pain rats.Methods Eighteen SD female rats weighing 180-220 g were randomly divided into 3 groups (n =6 each):A group(control group):intra-tibial injection of 3 μl saline;B group (model group):intra-periqueductal gray (PAG) injection of 0.5 μl saline after intra-tibial injection of 3 μl MRMT-1 cells (1 × 103/μl) ; C group (HS014 group):intra-PAG injection of 0.5 μl MC4R antagonist HS014 after intra-tibial injection of 3 μl MRMT-1 cells.From 1h of intra-tibial operation,0.5 μl saline or HS014 were injected into PAG respectively per day for 14 days.Heat threshold of rats' hind paws were measured every other day from one day before operation until 14 days later.The lumbar 4-6 spinal cord was removed on 14d after operation.The changes of the spinal glial fibrillary acidic protein (GFAP) immunoreactivity were detected by immunohistochemistry method.Results No significant differences in heat threshold were found at all time points in A group.During the first 6 days of postoperation there were obvious differences in heat stimulus between A and the other groups (P ＜ 0.05) ; During 7-14 d after operation,heat threshold in A and C group were significantly different from those of B group (P ＜ 0.05),but the differences were not remarkable between A and C group.The absorbance value of GFAP immunoreactivity in B group (59.46 ± 2.55) showed stronger staining than that in C group (50.15 ± 1.98) (P ＜ 0.05).No significant difference of GFAP immunoreactivity was found between C group and A group (P ＞ 0.05).Conclusion Intra-PAG injection of MC4R antagonist HS014 inhibits bone cancer pain in rats by repressing spinal astrocyte activation. Key words: Bone cancer pain;  Periaqueductal gray;  Melanocortin-4 receptor antagonist