Effective Prophylactic Treatments of Migraine Lower Plasma Glutamate Levels

Abstract

The role of glutamate in migraine treatment has not been much studied, even if this amino acid seems to be crucial in the pathogenesis of migraine. Our aim was to determine if there were differences in the plasma levels of glutamate between migraine patients and control subjects and if plasma levels of glutamate in migraine patients modified after 8 weeks of prophylactic treatment. We studied 24 patients with diagnosis of migraine without aura according to International Classification of Headache Disorders, 2nd edn criteria, and 24 age- and sex-matched healthy subjects, as controls. In migraineurs the level of glutamate was measured before and after 8 weeks of prophylactic treatment (topiramate 50 mg/day, five patients; amitriptyline 20 mg/day, seven patients; flunarizine 5 mg/day, seven patients; propranolol 80 mg/day, five patients). Venous blood samples were taken in the morning, after overnight fasting, and at least 3 days after the last migraine day. Glutamate levels were measured by means of a fluorimetric detector high-pressure liquid chromatographic method. Plasma levels of glutamate were significantly higher in migraine patients-either before (61.79 +/- 18.75 micromol/l) or after prophylactic treatment (17.64 +/- 5.08 micromol/l)-than in controls (9.36 +/- 2.1 micromol/l) (P < 0.05, anova followed by Newman-Keuls' test). After prophylactic treatment, with headache frequency reduced, plasma glutamate levels were significantly lower in the same patient with respect to the prior baseline level (P < 0.0001, Student's t-test for paired data), without any differences depending on the kind of prophylactic drug. Effective prophylactic treatments reducing high glutamate plasma levels found in migraine patients could act on the underlying mechanism that contributes to cause migraine. Plasma glutamate level monitoring in migraine patients might serve as a biomarker of response to treatments and as an objective measure of disease status.

Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis

“…In blood from interictal episodic migraine patients the pooled difference was not statistically significant (SMD: 1.08, 95% CI: -0.07, 2.22) (56)(57)(58)(59)(60)(61)(62). After exclusion of paediatric migraine patients (58), glutamate concentrations were increased in the (24).…”

Dementia, stroke and migraine — Some common pathological mechanisms

“…Elevated glutamate levels in the cerebrospinal fluid were measured during attacks in migraineurs, supporting the hypothesis of neuronal hyperexcitability in the disorder [122], and research data indicate that glutamate antagonists might be effective against the aura in FHM [123]; there are also observations regarding their usefulness in abolishing headache [124]. Topiramate a well-known glutamate antagonist, is effective in migraine prophylaxis [125] and any different effective prophylactic treatments lower the plasma glutamate level [126]. CSD, a hallmark of migraine aura, can also induce cytotoxic cell damage via glutamatergic mechanisms [118], leading to neuronal necrosis.…”

Influence of pro-algesic foods on chronic pain conditions

“…It has been found that mean baseline fasting plasma glutamate in 24 episodic migraine headache without aura patients was ~60 M as compared with ~ 10 M in 24 age and sexmatched controls [35] . Patients fasting plasma glutamate levels were reassessed 8 weeks after initiation of a migraine prophylactic therapy (topiramate, propranolol, amitriptyline, or flunarizine).…”

“…Multiple reports show that blood and salivary glutamate levels are elevated by 25-600% in migraine patients compared to healthy controls [31][32][33][34][35]. In addition, there is some evidence that glutamate levels in platelets are elevated in chronic tension-type headache sufferers [32].…”