Liang Xiping, Wang Sha, Qin Guangcheng, Xie Jingmei, Tan Ge, Zhou Jiying, McBride Devin W, Chen Lixue
Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, China.
Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Biomed Res Int. 2017;2017:7203458. doi: 10.1155/2017/7203458. Epub 2017 Mar 14.
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.
据报道，N-甲基-D-天冬氨酸（NMDA）受体亚基NR2B的酪氨酸磷酸化（NR2B-pTyr）会引发中枢敏化和脊柱持续性疼痛，但其在慢性偏头痛中的作用尚未得到研究。我们推测，NR2B的酪氨酸磷酸化通过大鼠降钙素基因相关肽（CGRP）促成慢性偏头痛（CM）。94只雄性Sprague-Dawley大鼠接受了7次炎性汤（IS）注射。在一部分动物中，通过蛋白质免疫印迹法和免疫荧光双重染色检测NR2B酪氨酸磷酸化的时间进程和位置。另一组动物分别给予金雀异黄素、赋形剂，或金雀异黄素与重组CGRP。测量机械阈值，使用蛋白质免疫印迹法定量NR2B-pTyr、NR2B和CGRP的表达，并采用硝酸还原酶法测量一氧化氮（NO）。CM后24小时，神经元中NR2B-pTyr表达达到峰值。金雀异黄素改善了机械阈值，并减少了CM后24小时和72小时的偏头痛发作。在CM大鼠模型中，NR2B的酪氨酸磷酸化通过上调CGRP表达降低了机械阈值并增加了偏头痛发作。因此，NR2B的酪氨酸磷酸化可能是治疗CM的潜在治疗靶点。
