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MRGPRX2 as a novel therapeutic target in headache

Shiva Nematgorgani1, Jane M Brandon1, Gregory Dussor1

  • 1Department of Neuroscience, The University of Texas at Dallas, Richardson, TX, United States; Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, United States.

Neurotherapeutics : the Journal of the American Society for Experimental Neurotherapeutics
|June 7, 2026
PubMed

Insights

The Mas-related G protein-coupled receptor X2/B2 (MRGPRX2/B2) on mast cells may drive migraine pathophysiology. Targeting this receptor could offer new therapeutic strategies for migraine.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Migraine is a prevalent neurologic disorder with substantial global impact.
  • Mast cells in the meninges are implicated in migraine pathophysiology.
  • The Mas-related G protein-coupled receptor X2/B2 (MRGPRX2/B2) is a key mediator in mast cell-neuron interactions.

Purpose of the Study:

  • To review recent findings on the role of MRGPRX2/B2 in migraine.
  • To explore the contribution of MRGPRX2/B2 to mast cell-sensory neuron communication.
  • To identify MRGPRX2/B2 as a potential therapeutic target for migraine.

Main Methods:

  • Review of current scientific literature on mast cells, MRGPRX2/B2, and migraine.
  • Analysis of neuropeptide-induced mast cell degranulation mechanisms.
  • Discussion of neuroimmune interactions in the meninges relevant to migraine.

Main Results:

  • Neuropeptides like substance P and PACAP activate mast cells via MRGPRX2/B2.
  • MRGPRX2/B2 activation leads to mast cell degranulation, neurogenic inflammation, and neuronal sensitization.
  • These processes contribute to the underlying mechanisms of migraine.

Conclusions:

  • MRGPRX2/B2 plays a critical role in mast cell and sensory neuron interactions in the meninges.
  • MRGPRX2/B2 represents a promising novel target for developing new migraine therapeutics.
Keywords:
HeadacheMRGPRX2MRGPRsMast cellsMigraine

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