O'Brien Melissa, Cairns Brian E
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; Center for Neuroplasticity and Pain, SMI®, Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, Aalborg E, Denmark.
Neuroscience. 2016 Oct 15;334:236-244. doi: 10.1016/j.neuroscience.2016.08.007. Epub 2016 Aug 11.
Ingestion of monosodium glutamate (MSG) has been shown to cause headaches in healthy individuals and trigger migraine-like headaches in migraine sufferers. We combined immunohistochemistry, in vivo electrophysiology, and laser Doppler recordings of dural vasculature to investigate the effect of systemic administration of MSG on the trigeminovascular pathway. Immunohistochemical analysis confirmed the expression of NMDA receptors on nerve fibers innervating dural blood vessels and excitatory amino acid transporter 2 on dural blood vessels. Systemic administration of MSG (50mg/kg) evoked an increase in ongoing discharge in 5/6 spinal trigeminal subnucleus caudalis (SpVc) neurons with dural input recorded from male and female rats, respectively, as well as lowering their mechanical activation threshold. There were no sex-related differences in these effects of MSG. Neuronal discharge and mechanical sensitization were significantly attenuated by co-injection with the peripherally restricted NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV) in both sexes. Systemic administration of MSG induced a 24.5% and 20.6% increase in dural flux in male and female rats, respectively. These results suggest that MSG-induced headache is mediated by the activation of peripheral NMDA receptors and subsequent dural vasodilation. Peripheral NMDA receptors are a potential target for the development of new drugs to treat headaches.
已证实，摄入味精（MSG）会使健康个体出现头痛，并引发偏头痛患者出现类似偏头痛的头痛。我们结合免疫组织化学、体内电生理学以及硬脑膜血管系统的激光多普勒记录，来研究全身给予味精对三叉神经血管通路的影响。免疫组织化学分析证实，支配硬脑膜血管的神经纤维上存在NMDA受体，硬脑膜血管上存在兴奋性氨基酸转运体2。全身给予味精（50mg/kg）分别使雄性和雌性大鼠记录到的5/6有硬脑膜传入的三叉神经尾侧亚核（SpVc）神经元的持续放电增加，并降低其机械激活阈值。味精的这些作用不存在性别差异。两性共同注射外周受限的NMDA受体拮抗剂（2R）-氨基-5-磷酸戊酸（APV）可显著减弱神经元放电和机械致敏作用。全身给予味精分别使雄性和雌性大鼠的硬脑膜血流量增加24.5%和20.6%。这些结果表明，味精诱发的头痛是由外周NMDA受体激活及随后的硬脑膜血管舒张介导的。外周NMDA受体是开发治疗头痛新药的潜在靶点。
