Several Compounds Identified as Potential Migraine Biomarkers

cerebrospinal fluid
cerebrospinal fluid
The compounds may potentially serve as good biomarkers for migraine.

Researchers have identified several biochemical compounds whose concentrations are altered in the cerebrospinal fluid (CSF) and blood of patients with migraine, suggesting that these compounds may be suitable targets for treatment.

Results of the meta-analysis were published in Cephalalgia.

While several compounds, including calcitonin gene-related peptide (CGRP), have previously been implicated in migraine pathophysiology, migraine is still not well understood. In this study, Robin M. van Dongen, of Leiden University Medical Center, the Netherlands, and colleagues sought to identify biochemical biomarkers in CSF of migraine patients, and assess the changes in presence in blood as well.

The study authors identified a total of 1197 research articles, of which 40 were considered eligible for analysis. This included 38 case-control studies and 2 case-crossover studies featuring patients with episodic and chronic migraine. Overall, 62 unique compounds have been identified in CSF of migraine patients. Compounds identified in 3 or more studies were glutamate, β-endorphin (β-EP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), CGRP, and nerve growth factor (NGF). Forty-four compounds were identified only once. Meta-analysis showed that glutamate, β-EP, CGRP, and NGF concentrations were consistently altered in CSF of migraine patients compared to controls.

CLINICAL CHART: Migraine and Headache Treatments

Glutamate concentrations in CSF were increased in patients with chronic migraine (SMD: 2.22, 95% CI: 1.30, 3.13), but data on blood concentrations was lacking. β-EP concentrations in CSF (SMD: – 1.37, 95% CI: –1.80, –0.94) and blood (SMD: –0.76, 95% CI: –1.17, –0.36) were decreased in patients with chronic migraine. Decreased concentrations were also seen in interictal and ictal patients. CGRP concentrations in CSF (SMD: 3.80, 95% CI: 3.19, 4.41) and blood (SMD: 0.70, 95% CI: 0.45, 0.95) were increased in chronic migraine patients, as well as in blood from ictal and interictal patients with episodic migraine. Concentrations of NGF were increased in CSF (SMD: 6.47, 95% CI: 5.55, 7.39) and blood (SMD: 1.08, 95% CI: 0.58, 1.59) of chronic migraine patients, however blood concentrations were not significantly different in interictal patients (SMD: 0.06, 95% CI: – 0.31, 0.42).

The authors note that high concentrations of NGF, glutamate, and BDNF are also present in other pain disorders like fibromyalgia, suggesting a shared mechanism. Further research, they said, should clarify the relevance of these biochemicals, and explore whether concentrations are altered across all migraine types, headache, and chronic pain disorders.


Van Dongen RM, Zielman R, Noga M, et al. Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis. Cephalalgia. 2016; doi: 10.1177/0333102415625614.