Role of JNK/MCP-1 signaling pathway in spinal cord in maintenance of bone cancer pain in rats

Objective To evaluate the role of c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) signaling pathway in the spinal cord in the maintenance of bone cancer pain (BCP) in rats.Methods Fifty female Sprague-Dawley rats,weighing 150-180 g,were randomly divided into 5 groups (n =10 each) using a random number table:sham operation group (group S),sham operation + JNK inhibitor SP600125 (group SP),BCP group,BCP + dimethyl sulfoxide (DMSO) group,and BCP+ SP600125 group (group BCP+ SP).BCP was induced by injecting Walker 256 mammary gland cancer cells into the bone marrow of the left tibia.On 10-12 days after BCP,SP600125 10 μg(10 μ1) was injected intrathecally once a day in SP and BCP + SP groups,and 5％ DMSO 10 μl was injected intrathecally once a day in BCP + DMSO group.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before BCP and 3,6,9,10,11 and 12 days after BCP.After measurement of MWT at 12 days after BCP,the rats were sacrificed and L4-6 segments of the spinal cord were removed for determination of MCP-1 expression by using immuno-histochemistry and Western blot.Results Compared with S group,MWT was significantly decreased at 6-12 days after BCP,MCP-1 expression was upregulated in BCP,BCP + DMSO and BCP + SP groups (P ＜ 0.01),and no significant change was found in the parameters mentioned above in SP group (P ＞ 0.05).Compared with BCP group,MWT was significantly increased at 10-12 days after BCP,MCP-1 expression was down-regulated in BCP + SP group (P ＜ 0.01),and no significant change was found in the parameters mentioned above in BCP + DMSO group (P ＞ 0.05).Conclusion JNK/MCP-1 signaling pathway in the spinal cord may be involved in the maintenance of BCP in rats. Key words: Bone neoplasms ;  Pain;  Mitogen-activated protein kinases ;  Chemokine CCL2 ;  Spinal cord