Effect of intrathecal CLP257 on bone cancer pain in rats

Abstract

Objective To investigate the effect of intrathecal CLP257 on the bone cancer pain in rats. Methods Forty adult female Sprague-Dawley rats, weighing 180-200 g, were divided into 4 groups(n=10 each)using a random number table: sham operation group(group S), bone cancer pain group(group BCP), dimethyl sulfoxide(DMSO)group, and CLP257 group.Bone cancer pain was induced by inoculating Walker 256 mammary gland carcinoma cell suspension(about 1×105 cells)10 μl into the medullary cavity of the left tibia.On 7th-9th days after establishment of the model, 5% DMSO 10 μl was injected intrathecally once a day in group DMSO, and 10 μg/μl CLP257 10 μl was injected intrathecally once a day in group CLP257.The mechanical paw withdrawal threshold(MWT)was measured on 1 day before establishment of the model(T0), on 1st-6th days after establishment of the model(T1-6), and at 4 h after intrathecal administration on 7th-9th days after establishment of the model(T7-9). After the last intrathecal administration, the L4-6 segments of the spinal cord were removed for determination of the expression of potassium chloride cotransporter 2(KCC2) protein and mRNA by Western blot and fluorescent quantitative real-time polymerase chain reaction, respectively. Results Compared with group S, the MWT was significantly decreased, and the expression of KCC2 protein and mRNA was down-regulated in BCP and DMSO groups, and the MWT was significantly decreased(P 0.05). Compared with group BCP, the MWT was significantly increased, and the expression of KCC2 protein and mRNA was up-regulated in group CLP257(P 0.05). Conclusion Intrathecal CLP257 can attenuate the bone cancer pain in rats. Key words: Thiazolidines; Pain; Bone neoplasms; Injections, spinal