PKC Contribute To Central Sensitization In A Rat Model Of Chronic Migriane

Background: Migraine is a common primary headache,with the characteristics of a recurrent headache with unilateral,throbbing,degree of moderate to severe and daily activities increased,accompanied by nausea,vomiting,photophobia and phonophobia.Migraine incidence is high,had serious impact on patients’ quality of work and life,it brings serious burden to individuals,families and society,which has been ranked as one of the most serious chronic functional disorder by WHO.Migraine headaches can be divided into episodic migraine(EM)and chronic migraine(CM)according to their frequency of attack.The clinical diagnostic criteria for chronic migraine were: 15 months of headache attack per month,lasting for three months with no drug abuse.Chronic migraine is a common complication of migraine,and approximately 2.5% of all cases of migraine are converted into chronic migraine.Compared with episodic migraine,chronic migraine has brought a more serious burden to the individual,family and society.So how to prevent chronic migraine is a major difficulty in the field of neurology.In recent years,many studies have found that central sensitization plays an important role in chronic migraine.Because of central sensitization is likely to be a major chronic factor of migraine,therefore,therapeutic strategies of chronic migraine that aim at the mechanism of central sensitization could be extremely useful,which is of great significance to improve the quality of life in patients with migraine.Previous studies have found that,in a variety of models of pain,the activity of PKC increased significantly,while inhibiting the activity of PKC can significantly reduce the pain,suggesting that PKC plays an important role in the process of central sensitization of pain.However,it remains unclear whether PKC is involved in the central sensitization mechanism of chronic migraine.The purpose of this paper is to investigate whether PKC participate in central sensitization in chronic migraine pathophysiological process.Methods:1、Sprague Dawley rats were randomly divided into 7 groups:A.Sham group(n=11),underwent 7 times PBS infusion.B.CM group(n=12),underwent 7 times IS infusion.C.CM+DMSO group(n=8),underwent 7 times IS infusion with DMSO injection.D.CM+CHE low-dose group(n=11),underwent 7 times IS infusion with CHE(4μg)injection.E.CM+CHE high-dose group(n=10),underwent 7 times IS infusion with CHE(8μg)injection.F.CM+PMA low-dose group(n=10),underwent 7 times IS infusion with PMA(100ng)injection.G.CM+CHE high-dose group(n=11),underwent 7 times IS infusion with PMA(200ng)injection.2、We made repeated infusions of inflammatory soup(IS)or PBS on the intact dura in awake rats to model the recurrent dural nociceptor activation assumed to occur in patients with chronic migraine(CM).3 、 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:1、Repeated infusions of IS decreased of pain threshold in the face and hindpaw region,up-regulated the expression of PKC,CGRP and c-Fos in TNC.2、Inhibition of PKC by CHE relieved the allodynia,reduced the expression of CGRP and c-Fos.3、Activation of PKC by PMA aggravated the allodynia,increased the expression of CGRP and c-Fos.Conclusion:1 、 Repeated administrations of IS nicely mimics the cutaneous allodynia and central sensitization seen in patients with CM.2、Inhibition and activation of PKC could regulate the pain threshold and the expression of CGRP and c-Fos,these dates indicated that PKC might play a prominent part in central sensitization of CM model.