Anti-nociceptive Effect Of Intrathecal SB203580 On Rats Of Bone Cancer Pain And Possible Mechanism

Part one: Effect of lntrathecal SB203580 in rats of bone cancer pain on mechanical hyperalgesiaObjective To investigate the effect of the specific p38MAPK inhibitor SB203580 in a rat model of bone cancer pain on mechanical withdraw threshold(MWT) of the injuried hind paw and the difference of weight bearing between hind paws.Methods Female SD rats weighing 150-170 g were used in this study.32 rats were randomly divided into 4 groups(n=8 each): sham group, model group, DMSO group and SB203580 group.Sham group inject normal sodium 5μl into tibia medullary cavity, other groups inject walker 256 cells (2×107/ml) 5μl into tibia medullary cavity; set pipes into subarachnoid space of all rats after establishing model 1d; DMSO group intrathecal inject DMSO (5%) 10μl, SB203580 group intrathecal inject SB203580 (1‰) 10μl, other two groups do not intrathecal inject anything after establishing model 10d. Response of the injuried hind paw to mechanical stimulation with von-Frey filament (MWT) and the difference of weight bearing between hind paws were measured before and after establishing model 1d,3d,5d,7d,10d and at 1,3,6,12 and 24 h after intrathecal SB203580 injection.Results The mechanical hyperalgesia emerged after estalishing model 7d and became more and more severe. After intrathecal SB203580 administration 1,3,6,12h MWT increased significantly, the difference of weight bearing between hind paws decressed significantly. 3~6h after intrathecal administration was the summit of SB203580 effect. Although at the summit, MWT and the difference of weight bearing between hind paws couldn't come back to the baseline.Conclusion Intrathecal administration of SB203580 can attenuate but cann't inhibit the mechanical hyperalgesia induced by bone cancer pain completely. Part two: Effects of lntrathecal SB203580 in a rat model of bone cancer pain on the express of pCREB in spinal cord dorsal hornObjective To observe the effect of the specific p38MAPK inhibitor SB203580 in a rat model of bone cancer pain on the express of pCREB in spinal cord dorsal horn, investigate the possible mechanism of anti-nociceptive effect of intrathecal SB203580 administration on rats of bone cancer pain.Methods Female SD rats weighing 150-170 g were used in this study. 24 animals were randomly divided into 4 groups(n=6 each): sham operation group, model group, DMSO group and SB203580 group. Sham group inject normal sodium 5μl into tibia medullary cavity, other groups inject walker 256 cells (2×10~7/ml) 5μl into tibia medullary cavity; set pipes into subarachnoid space of all rats after establishing model 1d; DMSO group intrathecal inject DMSO (5%) 10μl, SB203580 group intrathecal inject SB203580 (1‰) 10μl, other two groups do not intrathecal inject anything after establishing model 10d. The animals were killed at 6h after intrathecal SB203580 administration and L4,5 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immune-histochemistry.Results The express of pCREB in spinal cord dorsal horn was significantly increased after bone cancer pain.Intrathecal administration of SB203580 significantly inhibited the bone cancer pain-induced increase of pCREB expression.Conclusion Intrathecal administration of SB203580 can inhibite the pCREB express induced by bone cancer pain. The p38MAPK/CREB signal transduction pathway play an important role in bone cancer pain possiblely.