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AIM

To investigate the effects of herb-partitioned moxibustion (HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase (MEK)1, extracellular signal-regulated kinase (ERK)1/2 and cAMP response element binding protein (CREB) in spinal cord of rats with chronic inflammatory visceral pain (CIVP), and to explore the central mechanism of HPM in treating CIVP.

METHODS

Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide (DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu (ST25) and Qihai (CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor (p)MEK1, pERK1/2 and pCREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB mRNA in rat spinal cord were detected using real-time polymerase chain reaction.

RESULTS

Compared with the normal group, the AWR scores were increased significantly ( < 0.01) and the MWT and TWL scores were decreased significantly ( < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly ( < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups ( < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly ( < 0.01) and the MWT and TWL scores were increased significantly ( < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups ( < 0.01 or < 0.05). Compared with the model group, the expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups ( < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of pMEK1, pERK1/2 and pCREB proteins and the levels of MEK, ERK and CREB mRNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups ( < 0.01 or < 0.05).

CONCLUSION

HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and mRNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.

AIM

METHODS

RESULTS

CONCLUSION

目的

观察隔药灸对慢性内脏炎性疼痛（CIVP）大鼠脊髓丝裂原活化细胞外信号调节激酶（MEK）1、细胞外信号调节激酶（ERK）1/2和环磷酸腺苷反应元件结合蛋白（CREB）磷酸化的影响，探讨隔药灸治疗 CIVP 的中枢作用机制。

方法

雄性 SD 大鼠随机分为正常组、模型组、隔药灸组、假隔药灸组、MEK 抑制剂组和二甲亚砜（DMSO）组。采用三硝基苯磺酸和乙醇灌肠混合物制作 CIVP 模型。隔药灸组在双侧天枢（ST25）和气海（CV6）穴位进行隔药灸，假隔药灸组仅在相同穴位放置艾炷和药饼但不点燃。MEK 抑制剂组和 DMSO 组分别鞘内注射 L5-L6 部位的 U0126 和 30%DMSO。采用腹壁回缩反射（AWR）、机械缩足阈值（MWT）和热缩足潜伏期（TWL）评估疼痛行为。苏木精-伊红（HE）染色后观察结肠组织的形态学变化。采用 Western blot 检测大鼠脊髓磷酸化 MEK1（pMEK1）、磷酸化 ERK1/2（pERK1/2）和磷酸化 CREB（pCREB）的表达。采用实时聚合酶链反应检测大鼠脊髓中 MEK、ERK 和 CREB mRNA 的水平。

结果

与正常组比较，模型组、假隔药灸组和 DMSO 组 AWR 评分显著升高（ < 0.01），MWT 和 TWL 评分显著降低（ < 0.05）；与模型组比较，隔药灸组和 MEK 抑制剂组 AWR 评分显著降低（ < 0.01），MWT 和 TWL 评分显著升高（ < 0.05）；与假隔药灸组和 DMSO 组比较，隔药灸组和 MEK 抑制剂组 AWR 评分显著降低（ < 0.01），MWT 和 TWL 评分显著升高（ < 0.05）。与正常组比较，模型组、假隔药灸组和 DMSO 组大鼠脊髓 pMEK1、pERK1/2 和 pCREB 蛋白表达及 MEK、ERK 和 CREB mRNA 水平均显著升高（ < 0.01 或 < 0.05）；与模型组比较，隔药灸组和 MEK 抑制剂组大鼠脊髓 pMEK1、pERK1/2 和 pCREB 蛋白表达及 MEK、ERK 和 CREB mRNA 水平均显著降低（ < 0.01 或 < 0.05）；与假隔药灸组和 DMSO 组比较，隔药灸组和 MEK 抑制剂组大鼠脊髓 pMEK1、pERK1/2 和 pCREB 蛋白表达及 MEK、ERK 和 CREB mRNA 水平均显著降低（ < 0.01 或 < 0.05）。