PATHOPHYSIOLOGY, CLINICAL RESEARCH, NEW TREATMENTS, AND BASIC SCIENCE

Abstract

Both preclinical and clinical data link glutamate to the migraine pathophysiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age‐sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chronic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients. Comment: As noted in Ramadan et al's review and in this study, glutamate antagonists are an attractive target for migraine, confirmed in a proof of concept study published this year, Sang CN, Ramadan RM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein SD, Johnson KW, Phebus LS, Bleakman D, Ornstein PL, Arnold B, Tepper SJ, Vandenhende F. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well‐tolerated in acute migraine. Cephalalgia 2004;24:596‐602.—Stewart J. Tepper, MD