The Activation Of Extracellular Signal-regulated Kinase In The Rat Model Of Migraine And The Relationship Between Mast Cell Degranulation

Objective:To observe the expression of phosphorylated ERK(p-ERK) in the dura and nucleus trigeminalis caudalis in the nitroglycerin(GTN)-induced rat model of migraine ,and the relationship between the expression of p-ERK and mast cell degranulation.To reveal the role of p-ERK in the pathophysiology of migraine and provide new experimental basis for the treatment of migraine.Methods:72 male Sprague-Dawley rats were randomly devided into model group with migraine (n=54) and control group (n=18).Model group were subcutaneous injection of GTN(10mg/kg) to set up rat model of migraine,then the model group were randomly divided into three group:Compound48/80 group(intraperitoneal administration Compound48/80 2mg/kg); SCG+Compound 48/80 group (SCG i.p 10mg/kg prior to 48/80) and experimental control group (i.p the same dose of saline).Control group rats were subcutaneous injection of the same dose of saline.Model group were take dural mater and trigeminal nucleus caudalis at 15min,60min,120min after subcutaneous injection respectively Compound48/80,SCG+ Compound48/80 and saline.As a comparison,control group were take dural mater and trigeminal nucleus caudalis at 15min,60min,120min after subcutaneous injection same dose of saline.By immunohistochemical staining detected respectively the expression of phosphorylated ERK(p-ERK) in the dural and trigeminal nucleus caudalis of model group and control group.Result:1)Behavior observation :63 male SD rat inject GTN to induces migraine model,57 were succeeded,succeed rate is 90.4%.The GTN rat appeared reddish two ears,scratching head ,activity increasing at about 5～15min,peaked at 40～60min,keeped with 1～3h,then tiredly lie.The group of Compound48/80 and SCG+Compound48/80 has peak at 18～30min.Control group has scratching head at 15min,became to normalize.2)Microscopic observation : By immunohistochemical staining ,We found there are the expression of phosphorylated ERK(p-ERK) in contol group,s dural mater and trigeminal nucleus caudalis respectively at different time point.The expression of p-ERK is more in model group than control group at different time point,the group of C48/80 is most significant at 15min,and these positive immune reaction mainly distributed in the nearby of degranulated mast cell .3)Statistical result:Phosphorylation of ERK was found in the dural mater and trigeminal nucleus caudalis in both the model group and control group,but control group had no significant difference at different time point(P>0.05).And there was obviously more expression of p-ERK in the rat model of migraine at different time point than control group(P<0.05),The positive unit values of p-ERK at Compound 48/80 group at different time point was significantly higher than those in the SCG+Compound 48/80 group and experimental control group (P<0.05). The group of C48/80 is most significant at 15min than 60min and 120min(P<0.05).Conclusion: After subcutanceous GTN ,the expression of p-ERK in the the dural mater and trigeminal nucleus caudalis had increase,and changes with the number of mast cell degranulation,suggesting that ERK may be involved in the signal transduction of hyperalgesia in migraine, mast cell degranulation may be the reason of the high expression of p-ERK , and ERK signal transduction pathway plays an important role in the pathogenesis of migraine.The experimental result support trigeminovasular.