RESUMO
Objective To evaluate the changes in the activity of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord in a rat model of bone cancer pain (BCP).Methods One hundred and eight female Sprague-Dawley rats,weighing 160-180 g,were randomly divided into 3 groups (n =36 each):control group (group C):sham operation (group S) and group BCP.In group BCP Walker 256 mammary gland cancer cell suspension (1 × 105 cells/ml) 5 μl was injected into the left tibia,while in group S normal saline 5μl was injected into the left tibia instead of cancer cell suspension.Group C underwent no treatment.Mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) was measured at 1 day before inoculation and 3,5,7,14 and 21 days after inoculation.Six rats were sacrificed after the last measurement of MWT in groups C and S or after measurement of MWT at 3,5,7,14 and 21 days after inoculation in group BCP and the spinal cord was removed for determination of the expression of phosphorylated ERK5 (p-ERK5),ERK5 and Fos protein in the spinal dorsal horn by Western blot analysis.Results There was no significant difference in the MWT and expression of p-ERK5,ERK5 and Fos protein at each time point between groups C and S (P ＞ 0.05).Compared with groups C and S,MWT was significantly decreased at 7-21 days after inoculation,the expression of p-ERK5 and Fos protein was significantly up-regulated at 5-21 days after inoculation (P ＜ 0.05),and no significant change was found in the expression of ERK5 in group BCP (P ＞ 0.05).Conclusion Intra-tibial inoculation of Walker-256 breast cancer cells can increase the activity of ERK5 in the spinal cord in rats,leading to the increased release of Fos protein,thus inducing BCP.
