Effect of intrathecal injection of bovineadrenalmedulla 8-22 on pain behavior in a mouse model of bone cancer pain

Abstract

Objective To investigate the effect of intrathecal injection bovineadrenalmedulla 8-22 (BAM8-22) on pain behavior in a mouse model of bone cancer pain. Methods 50 male 8-10 week old C3H/HeJ mice weighing 18-22 g were divided randomly into 5 groups (n=8): sham group (S group), BCP group: artificial cerebrospinal fluid treat group(B0 group) and BAM8-22 treat groups (B1-B3 group). Group C and B were induced mouse models of bone cancer pain by intra-right-femur inoculations of osteolytic NCTC2472 cells while group S were injected only α-MEM. On the 14 d after inoculations, group S and BCP received intrathecal injection of artificial cerebrospinal fluid 5 μl, while group B1-B3 received intrathecal injection of BAM8-22 0.8, 2.4, 8.0 nmol, which dissolved in 5 μl artificial cerebrospinal fluid. They were intrathecally injected, respectively, once a day for 7 consecutive days starting from day 14 after inoculation. Mice received pain behavior tests including quantification of spontaneous flinches (NSF), paw withdrawal mechanical threshold (PWMT) 0.5 h before and at 2 h, after administration. Results Compared with S group [(1.80±0.20) times, (1.87±0.22) g], NSF [(14.67±2.65) times] was significantly increased (P=0.000) and MWT [(0.42±0.22) g] was significantly decreased (P=0.002) on 7-21 days after inoculation in BCP group. Compared with B0 group [(12.38±1.12) times, (0.48±0.22) g] and the basal level on 14th day before administration [(12.65±1.10) times, (0.46±0.19) g, P=0.012, 0.011, 0.001, 0.001], PWMT was significantly decreased, and NSF was increased at 2 h after administration in B2 group [(7.28±0.82) times, (1.01±0.13) g] and B3 groups [(4.18±1.02) times, (1.38±0.12) g, P=0.027, 0.025, 0.013, 0.009]. The analgesic effect of group B3 was more conspicuous compared with group B2 (P=0.007, 0.031). No obvious change of pain ethology indexes wag observed in group B1 [(12.03±1.22) times, (0.51±0.16) g] (P=0.096, 0.074, 0.527, 0.474). Conclusion Intrathecal BAM8-22 injection can effectively attenuated bone cancer pain with increased doses in the mouse model of bone cancer pain. Key words: Bone cancer pain; bovineadrenalmedulla 8-22; Behavior; Mouse