Effects of ketamine on glial activation in the lumbar spinal cord of the bone cancer pain rats

Abstract

Objective To investigate the effects of repeated administration of ketamine on glial activation in the lumbar spinal cord of the bone cancer pain rats.Methods Twenty-four SD female rats weighing 180-220 g were randomly divided into 4 groups (n =6 each):group A (control group),intra-tibial injection of 3 μl Hank' s solution; group B (model group),intra-tibial injection of 3 μl MADB-106 mammary gland carcinoma cells of rats (4.8 × 109/L) ; group C (ketamine 10 mg/kg) ; group D (ketamine mg/kg).The procedures in groups C and D were the same as those in the group B.From the 14th day of operation,ketamine (10 and 20 mg/kg,1 ml) was injected intraperitoneally into groups C and D respectively,and normal saline (1 ml) was injected into groups A and B per day for 4 days.Mechanical withdrawal thresholds and radiant heat threshold of rats' hind paws were measured every other day from one day before operation until 22 days later.The lumbar 4-5 spinal cord was removed on the 22nd day.The changes of the spinal glial fibrillary acidic protein (GFAP) and OX42 immunoreactivity were detected by immunohistochemistry strept avidin-biotin complex (SABC) method.Results No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in group A.During the first 6 days of post-operation there were obvious differences in radiant heat stimulus between group A and the other groups (P ＜0.05).During 14-22 days after operation,mechanical pain threshold and radiant heat threshold in groups B and C were significantly different from those in group A (P ＜ 0.05),but the differences were not remarkable between groups A and D.The GFAP and OX42 immunoreactivity in group B (57.05 ± 2.03 and 72.04 ± 2.25) and group C (52.02 ± 2.08 and 69.32 ± 2.14) in laminae Ⅰ-ⅣV of dorsal horn showed stronger staining than in group A (30.62 ± 1.06 and 42.34 ±3.16,P ＜0.05).No significant difference in GFAP and OX42 immunoreactivity was found between groups D and A (P ＞ 0.05).Conclusion Both astrocytes and microglia were activated ipsilaterally in the spinal cord of rats with MADB-106 mammary gland carcinoma cell-injected tibiae,and ketamine 20 mg/kg can repress this activation. Key words: Ketamine; Glial cell; Spinal cord; Bone cancer pain