Role of p38 mitogen-activated protein kinase In bone cancer pain in rats

Abstract

Objective To investigate the role of p38 mitogen-activated protein kinase(p38MAPK) in bone cancer pain in rats.Methods Fifty-six female SD rats weighing 150-170 g were randomly divided into 4 groups (n= 14 each): group ⅠNS operation; group Ⅱ bone cancer pain; group Ⅲ DMSO and group Ⅳ SB203580. Bone cancer pain was induced by injecting Walker256 mammary gland cancer cell suspension (107 cells/ml) 5 μl into the bone marrow of left tibia in group Ⅱ,Ⅲ and Ⅳ.5% DMSO 10 μl and SB203580 10 μg in 10 μl were injected IT in group Ⅲ and Ⅳ respectively at 10 days after bone cancer pain model was established. Paw withdrawal threshold to von Frey filament stimulation was measured before and at 1,3,5,7,10 d after bone cancer pain model was established and at 1,3,6, 12,24 h after IT DMSO or SB203580 injection. Six animals in each group were killed at 6 h after IT DMSO and SB203580 injection. The L_(4,5) lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal born by immuno-histochemistry. Results The rats developed hyperalgesia at 7 d after bone cancer pain had been induced. IT SB203580 significantly increased mechanical pain threshold. The number of pCREB positive neurons in the dorsal horn of L_(4,5) segment of the spinal cord was significantly increased by bone cancer pain. IT SB203580 significantly attenuated the increase in pCREB expression induced by bone cancer pain. Conclusion Intrathecal SB203580 can relieve the hyperalgesia induced by bone cancer pain and inhibit CREB phosphorylation in the spinal dorsal horn. p38MAPK signal pathway plays an important role in bone cancer pain. Key words: Bone neoplasms; p38 mitogen-activatod protein kinases; Injections; spinal