title: Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats.
abstract: 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.
authors.affiliation: Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Liang
authors.affiliation: Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Qin
authors.affiliation: Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Xie
authors.affiliation: Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Tan
authors.affiliation: Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Devin W
authors.initials: DW
authors.lastname: McBride
authors.affiliation: Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lixue
authors.identifier: 0000-0001-8213-8828
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D019833:Genistein / Q000008:administration & dosage; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D014443:Tyrosine; D002116:Calcitonin; D019833:Genistein; D015740:Calcitonin Gene-Related Peptide