MRGPRX2 as a novel therapeutic target in headache.

Migraine is a complex neurologic disorder with a significant global burden. Mast cells, a type of immune cell residing in the meninges and in close contact with dural afferent neurons, have been proposed to play an important role in the pathophysiology of migraine. While mast cells have been studied in the context of migraine for decades, more recent work has begun to investigate how the mast cell-specific receptor Mas-related G protein-coupled receptor X2/B2 (MRGPRX2/B2) may be an important contributor to neuroimmune interactions in migraine. Neuropeptides released from meningeal sensory neurons such as substance P and pituitary adenylate cyclase-activating polypeptide (PACAP), can induce mast cell degranulation via MRGPRX2/B2, leading to neurogenic inflammation and peripheral neuronal sensitization. In this review, we discuss recent findings on how MRGPRX2/B2 may contribute to mast cell and sensory neuron interactions in the meninges and could serve as a novel target for new migraine therapeutics.