Abstract: Objective To investigate the effect of different doses of Kinesin superfamily protein 17(KIF17) antisense oligodeoxynucleotide (ODN) on a mouse model of bone cancer pain. Methods fifty-five C3H/HeJ mice, aged 4~6 weeks, weighting 20~25g, were randomly divided into two groups: bone cancer pain group (group A, n=41) and sham operation group (group S, n=14). Group A was induced by implantation of 20μl α-minimal essence medium (α-MEM) which containing 2×105 osteosarcoma (NCTC 2472) cells into the intramedullary space of the right femur. And 20μl α-MEM with no cancer cell was injected instead in group S. The number of spontaneous flinches (NSF) and the paw withdrawal mechanical threshold (PWMT) were measured at the day before inoculation(base) and the days 4、7、10 and 14 after inoculation. According to the corresponding time points, ten mice were sacrificed, the lumbar segment of spinal cord (L3~5) was removed for determination the expression of KIF17 using Western blot. At the days 14 after inoculation, the mice of group A were randomly divided into four groups, KIF17 antisense ODN 2.5μg、5.0μg、10.0μg group (group A1-3) and the control group (group AC). Each group had nine mice. Group A1-3 were treated by intrathecal injection the corresponding dose of KIF17 antisense ODN, group S and AC was treated by saline. All the volume were 5μl. The pain behaviors were measured at 2、12、24、36 and 48 hours after administration and determinated the expression of KIF17. Results Compare with group S[(2.15±0.49)、(1.80±0.39)g]and the base[(2.08±0.34)、(1.88±0.35)g], the NSF[(11.95±0.78)]was significantly increased and PWMT[(0.34±0.11)g]was decreased at 14 days after inoculation in the bone caner pain groups (P<0.05);the expression of KIF17 were increased; Compared with group AC, the NSF[2h(4.80±0.40)]was decreased and the PWMT[2h:(0.95±0.33)g]was increased at 2、12、24 hours after administration in group A1 (P<0.05), and the NSF[2h:(2.35±0.26)、(2.53±0.21)]was decreased and the PWMT[2h: (1.70±0.32)g、(1.73±0.40)g]was increased at 2、12、24、36 hours after administration in group A2-3; group A2 compared with group A¬3, the NSF and PWMT were no statistically significant difference(P>0.05); After intrathecal administration, the expression of KIF17 was reduced in group A1-3(P<0.05). Conclusion Intrathecal KIF17 antisense ODN in the mice of bone cancer pain improved the pain behaviors, the analgesic effect and the action time related to the dose.
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