Intrathecal injection of NR2B antagonist ifenprodil alleviate the bone cancer pain in mouse

Objective To investigate the analgesic effect of intrathecal injection of NR2B antagonist ifenprodil in mouse of bone caner pain. Methods The mouse model of bone cancer pain was developed by intra-femur inoculations of α-minimal essence media (α-MEM) with osteolytic NCTC 2472 cells in C3H/HeJ mice(group T). The sham group (group S,n =10) were inoculated by α-MEM without any cells. 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 after inoculation to evaluate the mouse model of bone cancer. On the 14th d after inoculation, the succeed mouse model of bone cancer pain was divided randomly into 2.5 μg, 5 μg, 10 μg ifenprodil group(group I1, I2, I3,n =10) and solventia group (20%DMSO group, group C,n =10). Group I1～I3 were treated by intrathecal injection of corresponding dose of ifenprodil. Group C and group S were treated by intrathecal injection of solventia. All the volume of physic liquor of intrathecal injection was 5 μl. Pain ethology indexes mentioned above was observed at 2 h, 12 h, 24 h after administration. Results (1) The significant increasing of spontaneous lifting behaviors(13.16±1.78), the obvious decreasing of PWMT (0.47±0.19)g and PWTL (10.01±1.42)s were observed on 14th d after inoculation in group T compared with group S and preoperative base level( P ＜0.05). (2) The spontaneous lifting behaviors [I2:(9.00±1.80),(10.90±1.17);I3:(6.80± 2.51),(8.80±1.64)] was decreased, the PWMT [I2:(1.12±0.27)g,(0.82±0.30)g;I3:(1.44±0.34)g,(1.16±0.37)g] and PWTL [I2:(13.86±1.51)s,(12.12±1.27)s;I3:(15.95±1.70)s,(13.74±1.98)s] was increased in group I2 and I3 compared with the basal level on 14th d before administration and group C at 2 h and 12 h after administration ( P ＜0.05) The analgesic effect of group I3 was more conspicuous compared with group I2( P ＜0.05). No obvious change of pain ethology indexes was observed in group I1 ( P ＞0.05). Conclusion Intrathecal injection of ifenprodil can efficiently relieve mechanical hyperalgia and thermal hyperalgia in the mouse model of bone cancer pain. Key words: Ifenprodil;  NR2B;  Bone cancer pain;  Spinal cord