Targeting the Middle Meningeal Artery: Intra-Arterial Pharmacologic Strategies for Migraine Management

Background: The middle meningeal artery (MMA) plays a central role in migraine pathophysiology as a vascular and neuroimmune interface driving the throbbing pain. Inhibition of this cascade has been explored as a therapeutic approach, yet fewer than a dozen centers worldwide have published procedural or mechanistic data. Given the nascency of this field and the need for standardization, this review synthesizes the mechanistic and clinical evidence supporting intra-arterial pharmacologic modulation of the MMA for migraine treatment. Methods: A focused narrative review was conducted using limited but high-impact studies from pioneering groups exploring intra-arterial approaches to the MMA. Literature was arranged thematically and organized by the sites of cascade interruption and associated outcomes. Results: Since 2009, the use of intra-arterial therapies for severe headache syndromes has evolved from nimodipine for vasospasm-related headaches to verapamil for reversible cerebral vasoconstriction and, more recently, lidocaine for refractory or status migrainosus cases, sometimes with MMA embolization. Current research reframes migraines as an immunologically mediated neurovascular process, rather than purely a vascular or neuronal phenomenon. Recent studies have identified interleukins such as IL-1β, TNF-α, and IL-6 as key amplifiers of trigeminovascular activation, while emerging evidence implicates purinergic (P2X3, P2Y13) and PACAP/VIP pathways in modulating MMA excitability and neuropeptide release. Novel CGRP receptor antagonists, including zavegepant further reinforce the artery’s role as a therapeutic target. Conclusion: Our findings highlight a transition toward immune-modulating intra-arterial strategies, suggesting that future migraine therapies may increasingly focus on cytokine and neuroimmune signaling within the MMA rather than traditional vasodilatory control.