Effect of repeated intrathecal injection of ifenprodil on pain behaviors in mice with bone cancer pain

Objective To investigate the effect of ifenprodil in the mice of bone cancer pain. Methods 96 male C3H/HeJ mice were divided randomly into tumor group(Group T), control group(Group C)and sham group(Group S). The α-minimal essence media(α-MEM) with 2×105 osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to induce ongoing bone cancer related pain behaviors.The sham group was inoculated by α-MEM without any cells.On the 14th d after inoculation, pain ethology indexes such as the spontaneous lifting behaviors, the paw withdrawal mechanical threshold(PWMT) and the paw withdrawal thermal latency(PWTL)were observed on 1 d before inoculation and on 3 d, 5 d, 7 d, 10 d, 14 d, 17 d, 19 d, 23 d after inoculation.Lumbar intumescentia of mice in each group were taken out to investigate the expression level of NR2B western blot after pain behaviors tests at the same time point after intrathecal injection. Results (1) At day14 after the operation, the obvious increasing of spontaneous lifting behaviors((12.88±1.64)) and the expression of NR2B (2.12±0.13), the significant decreasing of PWMT((0.39±0.17)g) and PWTL((11.59±1.67)s) were observed in group T compared with group S and preoperative base level(P<0.05). (2) At day 17, day 19 and day 23 after the operation, compared with the basal level of day14 before administration and group C, the spontaneous lifting behaviors ((5.13±1.38), (4.70±1.58) , (5.64±1.17))of group T were obviously decreased, PWMT((1.10±0.65)g, (0.95±0.56)g, (1.05±0.26)g) and PWTL((15.17±1.27)s, (15.93±2.18)s, (16.28±1.48)s) were increased, the expression of NR2B((1.42±0.17), (1.67±0.53), (1.14±0.79)) were significantly decreased(P<0.05). Conclusion Repeated intratheal injection of ifenprodil can efficiently relieve spontaneous lifting behaviors, mechanical hyperalgia and thermal hyperalgia and decrease the expression of lumbar intumescentia NR2B in the mouse model of bone cancer pain. Key words: Ifenprodil; NR2B; Bone cancer pain; Mouse