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

Abstract

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.

Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization

“…Lending support to this notion are findings that serum levels of CGRP obtained from the external jugular vein are elevated in patients during migraine (with and without aura) [7, 11, 12]. In addition, increased CGRP levels have been reported in saliva and cerebrospinal fluid during migraine attacks [13, 14]. Further evidence of the involvement of CGRP in migraine is provided by data from clinical trials, in which triptans, acute anti-migraine drugs that block CGRP release [15, 16], and molecules that block activity of CGRP or its receptor could effectively alleviate headache pain [17].…”

Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

“…A recent systematic review and meta-analysis of migraine biomarkers has shown that CGRP in CSF and blood was elevated in chronic migraine patients (glutamate and NGF were also increased), and levels of the endogenous opiate β-endorphin decreased. 135 Preclinically, it has been shown that cortical spreading depolarization/depression (CSD) may trigger the release of neuropeptides such as CGRP 136 into the jugular vein and CSF from the primary trigeminal afferent fibers, 137 where it could promote sensitization of the trigeminal system. In contrast, there are findings 138 that suggest that acute activation of CGRP receptors may not play a key role in mediating CSD-evoked headache, but CGRP-mediated activation of meningeal afferents evoked by cortical efflux of potassium ion could promote headache.…”

Tyrosine Phosphorylation of NR2B Contributes to Chronic Migraines via Increased Expression of CGRP in Rats

“…Several lines of evidence support a central role of CGRP in migraine pathology [26–28]. Plasma CGRP levels, as well as CGRP cerebrospinal fluid levels, are increased during a migraine attack [18].…”