Monosodium glutamate alters the response properties of rat trigeminovascular neurons through activation of peripheral NMDA receptors. (15th October 2016)

• Record Type: Journal Article
• Authors: O'Brien, Melissa; Cairns, Brian E.
• Is Part Of: Neuroscience. Volume 334(2016)
• Page Start: 236
• Page End: 244
• Publication Date: 2016-10-15
• Subjects: ANOVA analysis of variance -- APV (2R)-amino-5-phosphonovaleric acid -- BBB blood–brain barrier -- CGRP calcitonin gene related peptide -- EAAT1-3 excitatory amino acid transporters 1-3 -- LSD least significant difference -- MMA middle meningeal artery -- MSG monosodium glutamate -- MT mechanical threshold -- NMDA N-Methyl-D-Aspartate -- NMDAr NMDA receptor -- SP substance P -- WDR wide-dynamic range; Doppler flowmetry -- dura -- nerve fibers -- sensory neuron -- trigeminal; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.08.007
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Dural blood vessels express NMDA receptors. MSG induces SpVc neuronal discharge and mechanical sensitivity to dural activation. APV, a peripherally restricted NMDA receptor antagonist, attenuates effects of MSG. Systemic administration of MSG induces dural blood vessel vasodilation. Blocking peripheral NMDA receptors may be useful in the treatment of headache. 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 (50 mg/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.