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October 13, 2012
1:00:00 PM - 4:00:00 PM
Room Hall C-Area J
Effect of Intrathecal Injection of Kinesin Superfamily Protein 17 Competitive Antagonist on Pain Behavior in a Mouse Model of Bone Cancer Pain
Zhengliang Ma, Ph.D., Fengling Wang, M.D., Xiaoping Gu, Ph.D., Kun Ni, M.D., Yu Zhou, M.D.
Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, China
Background It has been reported that N-methyl-D-aspartate (NMDA) receptor 2B subunit(NR2B) has a vital role in bone cancer pain, while the underlying mechanisms in detail are substantially unknown. KIF17 is a kinesin motor which transports NR2B. The aim of this study is to investigate the effect of intrathecal injection RC-13, a kinesin superfamily protein 17 competitive antagonist, on pain behavior in a mouse model of bone cancer pain.

Methods 40 male C3H/HeJ mice were randomly divided into tumor group (group T, n=32) and sham group (group S, n=8). Group T were induced mouse models of bone cancer pain by intra-right-femur inoculation of α-minimal essence media (α-MEM) with osteolytic NCTC2472 cells while group S were injected only α-MEM. Group T mice were further divided randomly into group Tc, group T1, group T2, and group T3 (n=8) at the 14th day after inoculation. Group S and group Tc were treated by injection of 10% DMSO. Group T1-T3 were treated by intrathecal injection of different doses of RC-13 dissolved in 10% DMSO, 2.5 μg/5 μl, 5 μg/5 μl, 10 μg/5 μl respectively. Each mouse accepted pain behavior tests including paw withdrawal mechanical threshold (PWMT) and spontaneous flinches (SF) before and at 3d, 5d, 7d, 10d, 14d. The same tests were performed at 1d, 3d, 5d, 7d after administration.

Results At the 7th day after the inoculation, compared with group S, PWMT of group T decreased significantly [(1.25±0.21)g VS (1.76±0.31)g)] (p<0.05) and SF increased significantly [(4.35±0.74) VS (1.96±0.62)] (p<0.05). And the pain behavior of tumor mice were aggravated along with the development of bone cancer. Compared with group Tc, treatment with RC-13 can dose-dependent attenuate the pain behaviors in groupT1, T2 and T3. The effect of RC-13 reached its peak at the 1st day, the qualification of PWMT of the three groups, which were (0.95±0.26)g, (1.1±0.28)g, (1.78±0.31)g, respectively, were significantly higher than group S [(0.34±0.16)g] (P<0.05); the spontaneous flinches, which were (7.65±1.44), (6.45±1.26), (4.25±0.72), respectively, were significantly lower than group S [(11.2±1.77)] (P<0.05). The antihyperalgesia effect of RC-13 in Group T3 could last for 5 days.Conclusion Intrathecal injection of RC-13 can efficiently relieve bone cancer pain.

Copyright © 2012 American Society of Anesthesiologists