Biomarkers associated with migraine and their potential role in migraine management.

Objective: The focus of this review is to review potential diagnostic and therapeutic biomarkers associated with migraine.

Background: Migraine headache is a common disease that affects millions of individuals worldwide. Although well-accepted diagnostic criteria exist for migraine, it is still a complex disorder that remains both underdiagnosed and misdiagnosed. The causes of migraine are likely a mix of genetic, epigenetic, and environmental factors that, together with the individual's life history, translate into the observed clinical heterogeneity. Inherent clinical heterogeneity is an obstacle in developing more effective treatments. The lack of appropriate biomarkers is also an impediment to developing more effective therapeutic/preventive approaches. Ultimately, biomarkers may facilitate the goal of individualized medicine by enabling clinicians to more accurately diagnose and treat migraine and other types of headache.

Methods: A comprehensive review was conducted of PubMed citations containing the key word "marker" OR "biomarker" combined with "migraine" OR "headache." Other key words included "serum," "saliva," "cerebrospinal fluid," "genes," "blood," and "inflammation." The only restriction was English-language publication. The abstracts of all articles meeting these criteria were reviewed, and full text was retrieved and examined for relevant references.

Results: Data from human studies have begun to identify genetic mutations/polymorphisms and altered levels of specific proinflammatory and neuromodulatory molecules that strongly correlate with migraine as well as symptom severity. Results from a smaller number of studies have identified parameters, such as the neuropeptide calcitonin gene-related peptide (CGRP), which are significantly associated with response to specific treatments for acute migraine attacks and prophylaxis. Epigenetic mechanisms may also be involved in the development of migraine, and understanding environmentally induced genetic changes associated with this disease may eventually guide the development of therapies capable of reversing these pathophysiological changes in gene function.

Conclusions: The understanding of the etiology of migraine is incomplete. Although the identification and validation of biomarkers has greatly advanced diagnostic precision and measures of therapeutic efficacy in other diseases, there are no currently accepted biomarkers for chronic or episodic migraine. However, the continued investigation and identification of genetic, epigenetic, and molecular biomarkers is likely to facilitate the goal of individualizing medicine by enabling clinicians to more accurately diagnose and treat migraine and other headache disorders.