Molecular Mechanisms of Glucocorticoid Action in Migraine: A Systematic Review of Neuroinflammatory and Vascular Pathways.

Migraine is a prevalent neurological disorder with complex pathophysiology that involves neurogenic inflammation, vasodilation, and hypersensitization of the trigeminovascular system. Recently, glucocorticoids have attracted attention as adjunctive treatments for migraine, mainly in refractory or recurrent attacks. Although they are traditionally recognized for their anti-inflammatory effects, the specific molecular mechanisms by which glucocorticoids alleviate migraine symptoms are not yet fully understood. In this study, we systematically reviewed the literature from 2004 to 2024 to evaluate the molecular mechanisms by which glucocorticoids exert their therapeutic effects in migraine. The analysis focused mainly on their impact on neuroinflammatory mediators, the integrity of the blood-brain barrier, and nociceptive signaling. Results from 26 selected articles showed that glucocorticoids decreased the expression of matrix metalloproteinase-9 (MMP-9), inhibited nitric oxide synthesis, and reduced calcitonin gene-related peptide (CGRP) levels, all of which are key agents implicated in migraine pathogenesis. Furthermore, glucocorticoids modulate transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1), reduce the production of pro-inflammatory cytokines like interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), and limit prostaglandin synthesis via cyclooxygenase-2 (COX-2) inhibition. These pathways suppress central and peripheral sensitization, which provides symptom relief. Our findings suggest that glucocorticoids play a more significant role in migraine management than previously appreciated. This influences neuroimmune responses and vascular permeability. These insights state the therapeutic potential of glucocorticoids beyond general inflammation control and encourage more targeted clinical use. This is especially true in cases with neuroinflammatory features.