title: Monosodium glutamate alters the response properties of rat trigeminovascular neurons through activation of peripheral NMDA receptors.
abstract: 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.
authors: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
authors: Melissa
authors: M
authors: O'Brien
authors: 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. Electronic address: brian.cairns@ubc.ca.
authors: Brian E
authors: BE
authors: Cairns
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004388:Dura Mater / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D008297:Male; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012684:Sensory Thresholds / Q000187:drug effects; D012727:Sex Characteristics; D012970:Sodium Glutamate / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014110:Touch / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D027342:Excitatory Amino Acid Transporter 2; D016194:Receptors, N-Methyl-D-Aspartate; C493395:Slc1a2 protein, rat; D014665:Vasodilator Agents; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D012970:Sodium Glutamate
keywords: Doppler flowmetry; dura; nerve fibers; sensory neuron; trigeminal