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目的:观察脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(pCREB,phosphorylated cAMP re-sponse element binding protein)在骨癌痛大鼠中的表达变化,探讨其在骨癌痛中枢敏化中的作用。方法:雌性SD大鼠32只,随机分为4组(n=8),分别为对照组,骨癌痛6d、12d、18d组。对照组和骨癌痛各组分别于左胫骨上端注射Hank’s液和Walker256肿瘤细胞5μl。分别于术前(基础值)、术后6d、12d、18d测定机械性痛阈值。对照组于术后18d,其余三组在各时点测定机械性痛阈值后立即处死大鼠,取L4~L6脊髓组织,采用免疫组化法计数pCREB免疫反应阳性细胞数量。结果:骨癌痛术后6d、12d、18d组机械性痛阈值进行性下降(P<0.01),对照组差异无统计学意义(P>0.05);与对照组比较,骨癌痛术后6d、12d、18d组脊髓pCREB免疫反应阳性细胞数逐渐增多(P<0.01)。结论:骨癌痛大鼠脊髓背角pCREB表达的增加,可能是产生中枢敏化的机制之一。
OBJECTIVE: To observe the expression changes of phosphorylated cAMP re-sponse element binding protein (pCREB) in rat spinal cord dorsal horn and explore its central sensitization in bone cancer pain. effect. Methods: Thirty-two female SD rats were randomly divided into 4 groups (n=8), which were control group and bone cancer pain group 6d, 12d and 18d respectively. The control group and the bone cancer pain group were injected with Hank’s solution and Walker256 tumor cells 5 μl at the upper end of the left tibia. The mechanical pain thresholds were measured before operation (basal values), 6 days, 12 days, and 18 days after operation. The rats in the control group were sacrificed at the 18th day after the operation, and the mechanical pain threshold was measured at each time point. The spinal cord tissues of L4~L6 were used to count the number of pCREB immunoreactive cells by immunohistochemistry. RESULTS: The mechanical pain thresholds of 6 days, 12 days, and 18 days after bone cancer pain were progressively decreased (P<0.01). There was no significant difference in the control group (P>0.05). Compared with the control group, 6 days after the bone cancer pain. The number of pCREB immunoreactive cells in the spinal cord increased gradually in the 12-day and 18-day groups (P<0.01). Conclusion: The increase of pCREB expression in spinal dorsal horn of rats with bone cancer pain may be one of the mechanisms of central sensitization.