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BioMed Research International
Volume 2017, Article ID 7203458, 8 pages
Research Article

Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats

1Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China
2Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
3Chongqing Key Laboratory of Neurology, Chongqing, China
4Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

Correspondence should be addressed to Lixue Chen; nc.ude.umqc.latipsoh@euxilnehc

Received 18 October 2016; Revised 14 December 2016; Accepted 8 February 2017; Published 14 March 2017

Academic Editor: Gang Chen

Copyright © 2017 Xiping Liang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tyrosine phosphorylation of NR2B (NR2B-pTyr), a subunit of the N-methyl-D-aspartate (NMDA) receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM) through calcitonin gene-related peptide (CGRP) in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining. Another set of animals were given either genistein, vehicle, or genistein and recombinant CGRP. The mechanical threshold was measured, the expressions of NR2B-pTyr, NR2B, and CGRP were quantified using western blot, and nitric oxide (NO) was measured with the nitric acid reductase method. NR2B-pTyr expression, in neurons, peaked at 24 hours after CM. Genistein improved the mechanical threshold and reduced migraine attacks 24 and 72 hours after CM. Tyrosine phosphorylation of NR2B decreased the mechanical threshold and increased migraine attacks via upregulated CGRP expression in the rat model of CM. Thus, tyrosine phosphorylation of NR2B may be a potential therapeutic target for treatment of CM.