Objective: The purpose of this paper is to investigate whether PKC participates in central sensitization in chronic migraine pathophysiological process.Methods:Sprague-Dawley rats were randomly divided into 7 groups: Sham group (n=11), CM group (n=12), CM+DMSO group (n=8), CM+CHE4 μg group (n=11), CM+CHE 8 μg group (n=10), CM+PMA100 ng group (n=10), CM+PMA 200 ng group (n=11). We repeatedly infused inflammatory soup (IS) on the intact dura in awake rats to model the recurrent dural nociceptor activation assumed to occur in patients with chronic migraine (CM). PKC blocker chelerythrine chloride (CHE) and PKC activator Phorbol 12-myristate 13-acetate (PMA) were administrated to investigate the role of PKC in central sensitization induced by inflammatory soup. Then we used von Frey test to detect the change of pain threshold. Western blotting was performed to detect the expression of PKC, CGRP and c-Fos in trigeminal nucleus caudalis (TNC).Results:Repeated infusion of IS decreased pain threshold in the face and hindpaw region, and up-regulated the expression of PKC, CGRP and c-Fos in TNC. Furthermore, inhibition of PKC by CHE relieved the allodynia, and reduced the expression of CGRP and c-Fos. Activation of PKC by PMA aggravated the allodynia, and increased the expression of CGRP and c-Fos. Conclusion:Inhibition and activation of PKC could regulate the pain threshold and the expression of CGRP and c-Fos. These data indicate that PKC might play a prominent part in central sensitization of CM model.%目的:本文旨在研究蛋白激酶C(PKC)是否通过中枢敏化参与慢性偏头痛病理生理过程.方法:SD雄性大鼠随机分为7组,假手术组(n=11),模型组(n=12),模型+溶剂组(n=8),PKC抑制剂4μg组(n=11),PKC抑制剂8μg组(n=10),PKC激动剂100 ng组(n=10),PKC激动剂200ng组(n=11)."炎性汤"反复刺激硬脑膜,模拟硬脑膜痛觉感受器的反复激活,建立慢性偏头痛大鼠模型,侧脑室给予PKC抑制剂和PKC激动剂,使用von Frey test测定大鼠面部及后足的机械痛阈值,Western blot检测PKC、CGRP、c-Fos蛋白的表达变化.结果:"炎性汤"反复刺激硬脑膜后,大鼠面部及足底的机械痛阈值显著降低,而三叉神经脊束尾核部位的CGRP、c-Fos及PKC蛋白表达显著增加.使用CHE抑制PKC可以显著增高大鼠面部及足底痛阈值,显著降低CGRP、c-Fos的表达;而使用PMA激活PKC则降低痛阈值,显著增高CGRP、c-Fos的表达.结论:本研究表明PKC可以调节机械痛阈值以及CGRP、c-Fos的表达变化,提示PKC参与慢性偏头痛中枢敏化的病理生理过程.
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