Analgesic efficacy of intrathecal injection of competitive kinesin superfamily protein 17 antagonist in a mouse model of bone cancer pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the analgesic efficacy of intrathecal injection of RC-13,a competitive kinesin superfamily protein 17 antagonist,in a mouse model of bone cancer pain.Methods Forty male C3H/HeJ mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 5 groups (n=8 each) sham operation group (group S); bone cancer pain + 5 μl dimethyl sulfoxide (DMSO) group (group R0); bone cancer pain + 2.5 μg RC-13 group (group R1); bone cancer pain + 5 μg RC-13 group (group R2) and bone cancer pain + 10 μg RC-13 group (group R3).In groups R0-3,bone cancer pain was induced by implantation of α-min-imal essence medium (α-MEM) containing osteosarcomaNCTC 2472 cells into the intramedullary space of right femur.In group S,culture medium α-MEM containing no cancer cell was injected instead.10％ DMSO 5 μl and RC-13 2.5 μg/5 μl,5μg/5μ1 and 10 μg/5 μ1 dissolved in 10％ DMSO were injected intrathecally in groups R0-3,respectively,once a day for 3 consecutive days starting from 14th day after inoculation of the tumor cells.Pain behavior was assessed by the paw withdrawal mechanical threshold (PWMT) and spontaneous lifting times (SLTs) measured at 1 day before inoculation and at 3,5,7,10,14 days after inoculation.The same tests were also performed at 1,3,5 and 7 days after administration in groups R0-3.Results Compared with group S,PWMT was significantly decreased and SLTs were increased at 7-14 days after inoculation in the other groups (P ＜ 0.05).Compared with group R0,PWMT was significantly increased and SLTs were reduced at 1 day after administration in group R1,at 1and 3 days after administration in group R2,and at 1,3 and 5 days after administration in group R3 (P ＜ 0.05).Compared with group R1,PWMT was significantly increased and SLTs were reduced at 3 days after administration in group R2,and at 1,3 and 5 days after administration in group R3 (P ＜ 0.05).Compared with group R2,PWMT was significantly increased and SLTs were reduced at 1 and 3 days after administration in group Rs (P ＜ 0.05).Conclusion Intrathecal RC-13,a competitive kinesin superfamily protein 17 antagonist,has a good analgesic efficacy in a mouse model of bone cancer pain and the efficacy is dose-dependent.