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MIGRAINE: PATHOPHYSIOLOGY
Publication year - 2004
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2004.t01-4-04025.x
Subject(s) - migraine , tolerability , cortical spreading depression , glutamate receptor , neuroscience , medicine , ampa receptor , neurology , nmda receptor , ketamine , glutamatergic , trigeminal ganglion , pharmacology , anesthesia , psychology , receptor , adverse effect , sensory system
Migraine pain‐relay centers, including the trigeminal ganglion, trigeminal nucleus caudalis, and thalamus, contain glutamate‐positive neurons, and glutamate activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical spreading depression, trigeminovascular activation and central sensitization. Glutamate receptor subtype antagonists are effective preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic sysem, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies. Comments: Dr. Ramadan, who is now vice president of Clinical and External Affairs and Professor of Neurology at Finch University of Health Sciences/The Chicago Medical School, championed the systematic search for an effective glutamate antagonist for migraine when he wasa medical advisor in neuroscience research at Eli Lilly. He believed that a glutamate ampa‐kainate antagonist might be the way to go (Sang CM, Ramadan NM, Chappell AS, et al. A double‐blind, placebo‐controlled study to investigate the efficacy and tolerability of intravenous 1.2 mg/kg LY293558 vs. 6 mg subcutaneous sumatriptan vs. placebo in patients with an acute migraine attack [abstract]. Neurology. 2001;56(suppl 3):A219). This review is a great place to start to understand the thinking that makes glutamate an excellent future therapeutic target in migraine. SJT