骨癌痛大鼠脊髓背角pCREB表达的变化

CHANGES IN EXPRESSION OF PHOSPHORYLATED CYCLIC AMP RESPONSE ELEMENT BINDING PROTEIN(pCREB) IN DORSAL HORN OF SPINAL CORD IN A RAT MODEL OF BONE CANCER PAIN

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 investigate the expression of phosphorylated cyclic AMP response element binding protein（pCREB） in the dorsal horn of spinal cord in rats with bone cancer pain.Methods： 32 female SD rats were randomly divided into 4 groups（n=8 each）： control group（intra-tibial injection of 5μl Hank＇s solution）;bone cancer pain（intra-tibial injection of 5μl Walker-256 mammary gland carcinoma cells of rats） 6 d,12 d and 18 d group.The paw withdraw threshold was measured before operation and on day 6,12 and 18 after operation.The animals were killed on day 6,12 and 18 after operation.The lumbar 4~6 of spinal cord was immediately removed.The pCREB expression was measured by immunohistochemistry.Results： The mechanical pain thresholds in rats of bone cancer pain 6 d,12 d and 18 d group were significantly decreased.No significant change of mechanical pain thresholds was observed in control group.The expression of pCREB in the spinal cord was gradually increased in bone cancer pain 6 d,12 d and 18 d group as compared with the control group.Conclusion： The increase in the expression of pCREB in the spinal cord is involved in the mechanism of central sensitization in the bone cancer pain.