| Background: Migraine is one of the most common primary headaches;it is defined as attacks of moderate to severe pulsating and mostly unilateralheadache. It can divided into episodic migraine and chronic migraineaccording to the frequency of recurring headache. Chronic migrainedefined as headache occurring on15or more days per month for more than3months, which has the features of migraine headache on at least8daysper month, without medication overuse. It is common headache andpopulation-based studies suggest that1-3%of the general population sufferfrom CM. It is estimated that migraine patients transit from episodicmigraine (EM) to CM at a rate of2.5%of patients per year. World HealthOrganization had confined chronic migraine as one of seven disablerdiseases.The physiopathology of chronic migraine was still unclear. Themajority views of present studies hold that chronic migraine had closelyrelationship with central sensitization which induced by neurogenicinflammation. Activation of the N-methyl-D-aspartate receptor (NMDAR),caused by neurogenic inflammation, is critical for the maintenance of pain. Phosphorylation of NMDAR NR2B subunit is required for activation ofNMDAR and also is the main reason of maintenance pain.With in-depth research of migraine, the relationship between migraineand Calcitonin gene related peptide (CGRP) was found. Study found thatthe CGRP, trigeminal microvascular activation markers, was increased inthe plasma and cerebrospinal fluid of migraine patients.Central sensitization caused by neurogenic inflammation hadrelationship with migraine. Activation of NMDAR play important role topain maintain, which induced by inflammation. Tyrosine phosphorylationof NR2B (NR2B-Tyr) determines the activation of NMDAR. CGRP playimportant role in migraine. We therefore hypothesized that NR2B involvedin pathogenesis of migraine through NR2B-Tyr/CGRP pathway followingmigraine rats.Methods:56Sprague-Dawley (SD) rats were randomly divided intosix groups:A. Sham: administration with PBS;B. CM: administration with inflammatory soup (IS) and Glycerintrinitrate (GTN);C. CM+vehicle: administration with IS, GTN and PBS;D. CM+genistien (0.01μl/kg): administration with IS, GTN andgenistien (0.01μl/kg);E. CM+genistien (0.1μl/kg): administration with IS, GTN and genistien (0.1μl/kg);F. CM+genistien+CGRP: administration with IS and TGN for themodle, and then treatment with genistien (0.1μl/kg) and CGRP。Observe behavior change and paw withdrawal threshold to test effectof treatment. And drew blood to detect the concentration of CGRP and NOin plasma. Use western blot and immunohistochemistry to detect NR2Band tyrosine phosphorylation of NR2B expression in trigeminal nucleuscaudalis.Results: C group scratched their heads more frequently than A group(P≤0.05). Paw withdrawal threshold was decreased in C group comparedwith A group (P≤0.05). Treatment with high dosage of genistein (E group)significantly improve paw withdrawal threshold and decreased thefrequency of scratching their heads compared to C group (P≤0.05).From western blot result, we found that the protein level of NR2Btyrosine phosphorylation was increased in C group compared to A group(P≤0.05). Treatment with genistein (0.1μl/kg), E group, had lower proteinlevel of NR2B tyrosine phosphorylation (P≤0.05). There was no differentchange in NR2B protein level. Consistent with western blot result, CGRPand NO was increased in C group (P≤0.05). Inhibition of NR2B tyrosinephosphorylation decreased CGRP and NO level (P≤0.05). This protectivefunction was revised in F group.Immunohistochemical result revealed that more NR2B tyrosine phosphorylation positive cells colocalized with neurons in B groupcompare to A group.Conclusion: The recurrent migraine model used to imitate chronicmigraine was induced by IS and GTN; NR2B tyrosine phosphorylationinvolved in chronic migraine. NR2B involved in chronic migraine thoughNR2B tyrosine phosphorylation/CGRP pathway. |
PDF Full Text Request