Expression of spinal PD-L1 in bone cancer pain model mice and its effect on pain behaviors / 中华行为医学与脑科学杂志

ABSTRACT

Objective To evaluate the role of programmed cell death ligand-1 (PD-L1) in a mouse model of bone cancer pain.Methods Ninety-six male C3H/HeN mice (20-25 g,4-6 weeks old),which inoculated with osteolytic NCTC 2472 cells,were used to build the model of bone cancer pain.Part onesixtyfour male C3H/HeJ mice were randomly divided into sham group (group Sham,n =32) and tumor group (group Tumor,n=32).Part twoTwenty-four male C3H/HeJ mice which were inoculated with osteolytic NCTC 2472 cells were randomly divided into group T (tumor,n=8),group PD-L1 (intrathecal injection with PLX3397,1 μg/5μl,n=8) and group NS (intrathecal injection with normal saline,n=8).Also,there were eight male C3H/HeJ mice in group S which were intra-femur inoculated with α-MEM.The pain behaviors of Sham group and Tumor group were observed and the expression of PD-L1 was detected before inoculation and on 4,7,10,14 and 21 days after inoculation,including paw withdrawal mechanical threshold (PWMT) and the number of spontaneous flinches (NSF).On 14 d after inoculation,the mice of group PD-L1 and group NS were intrathecal injected with drugs respectively.Pain behaviors were observed before injection and 2,4,6,24h after injection.Results Compared with group Sham,PWMT was significantly decreased and NSF was increased on 7～ 21 d after inoculation in group Tumor (P＜0.05).Compared with baseline and group S (baseline (0.38±0.06),group Sham (0.35±0.08),(0.38±0.08),(0.36±0.07)),the expression of PDL1 was up-regulated on 10-21 d after inoculation in group Tumor ((0.77±0.06),(1.21±0.04),(1.18±0.06)) (P＜0.05).Compared with group NS,PWMT was significantly increased (group NS (0.25t0.12),(0.25±0.12),(0.31±0.12),group PD-L1 (1.43±0.49),(1.35±0.44),(0.95±0.26)),and NSF was decreased on 2-6 h after injection in group PD-L1 (group NS(11.74± 1.31),(13.78±0.0.91),(13.63±1.06),group P D-L1 (4.90± 0.82),(4.15± 0.71),(7.65±0.56)) (P＜0.05).Conclusion Expression of PD-L1 in spinal cord was up-regulated in the mouse model of bone cancer pain.Intrathecal injection of recombinant PD-L1 has an analgesic effect on mice with bone cancer.