Changes in innate immunity in chronic migraine. Role of Toll-like receptors 2 and 4 as key players in migraine chronification and potential therapeutic targets

Abstract

Migraine is a complex disorder that involves several physiopathological mechanisms. Toll-like receptors (TLRs) are involved in neuroinflammation, but their role in migraine is not completely understood. This translational study investigates whether expression of Toll-like receptors 2 and 4 (TLR2 and TLR4) is increased in chronic migraine (CM) patients, and if TLR4 is involved in the vascular response to CSD. With this aim, we designed a clinical cross-sectional study measuring peripheral blood expression of TLR2 and TLR4 and a experimental study based on an animal model of cortical spreading depolarization (CSD). CM patients showed increased expression of TLR4 and TLR2 in peripheral blood. TLR4 KO mice had a different response to CSD stimulation that was reproduced after pharmacological blockade of TLR4. Our results suggest that TLR2 and TLR4 may have a role in migraine pathophysiology, providing a potential novel strategy for treatment.