Glutamate Levels in Cerebrospinal Fluid and Triptans Overuse in Chronic Migraine

Vieira, Domingos Sávio deSouza; Naffah-Mazzacoratti, Maria da Graça; Zukerman, Eliova; Soares, Carlos Augusto Senne; Cavalheiro, Ésper A.; Peres, Mário Fernando Prieto

doi:10.1111/j.1526-4610.2007.00812.x

Cited by 49 publications

(43 citation statements)

References 33 publications

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“…Gluatamate, the major excitatory neurotransmitter in CNS plays a key role in the trigeminovascular activation, especially in central sensitisation via activation of NMDA receptors [18, 19]. Glutamate appears to be involved in nociception since glutamate is expressed in the trigeminal ganglion and other sensory ganglia [20, 21].…”

Section: Discussionmentioning

confidence: 99%

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72)

et al. 2017

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BackgroundMigraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund’s Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72.MethodsActivation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord.ResultsWe found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration.ConclusionThis is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

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Section: Discussionmentioning

confidence: 99%

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72)

et al. 2017

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“…Primarily the latter is hypothesised to contribute to chronic sensitisation of central neurons (i.e. in the nucleus trigeminus) (19)(20)(21)(22). It is believed that this process also occurs in other chronic pain disorders such as fibromyalgia, where increased CSF concentrations of NGF, BDNF and glutamate have been found (21).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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Objective: To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods: We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results: Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased b-endorphin (b-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and b-EP (chronic, interictal and ictal) was decreased. Conclusions: Glutamate, b-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

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“…These also include measurements of CSF concentrations of different amino acids and related metabolic compounds [34,37,38] . Especially CSF levels of glutamate have been studied in these populations [37,38] .…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Concentrations of Functionally Important Amino Acids and Metabolic Compounds in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

et al. 2010

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Cerebrospinal fluid (CSF) biomarkers play an important role in the differential diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and its postulated precursor stage mild cognitive impairment (MCI). While CSF tau protein, phospho-tau protein and β-amyloid have become part of the diagnostic process in clinical routine, the importance of several other biomarkers remains quite unclear. Among these, amino acids and metabolic compounds have been studied in clinical conditions mostly other than AD and, to our knowledge, never in MCI. In patients with AD (n = 14) and MCI (n = 13) we now determined CSF levels of 36 different amino acids and metabolic compounds by high-performance liquid chromatography. We found that 8 out of 36 amino acids (urea, threonine, glutamate, citrulline, α-aminobutyric acid, ornithine, ammonia and arginine) were significantly elevated in the CSF of patients with AD compared to those with MCI. As most of these amino acids and metabolic compounds are functionally important for brain-specific metabolic processes, neurotransmitter pathways or compensatory mechanisms, our findings might reflect these changes occurring within the brain of patients with MCI and those who developed manifest AD.

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Glutamate Levels in Cerebrospinal Fluid and Triptans Overuse in Chronic Migraine

Abstract: Our study showed lower glutamate levels in CSF of CM patients overusing triptans. Glutamate may be implicated in triptan response mechanisms, triptans may work in part by reducing extracellular glutamate levels in the brain.

Cited by 49 publications

References 33 publications

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72)

Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72)

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

Cerebrospinal Fluid Concentrations of Functionally Important Amino Acids and Metabolic Compounds in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

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