A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain

Dustin P. Green, Nathachit Limjunyawong, Naina Gour, Priyanka Pundir, Xinzhong Dong

Research output: Contribution to journalArticle

Abstract

Mast cells can be found in close proximity to peripheral nerve endings where, upon activation, they release a broad range of pro-inflammatory cytokines and chemokines. However, the precise mechanism underlying this so-called neurogenic inflammation and associated pain has remained elusive. Here we report that the mast-cell-specific receptor Mrgprb2 mediates inflammatory mechanical and thermal hyperalgesia and is required for recruitment of innate immune cells at the injury site. We also found that the neuropeptide substance P (SP), an endogenous agonist of Mrgprb2, facilitates immune cells’ migration via Mrgprb2. Furthermore, SP activation of the human mast cell led to the release of multiple pro-inflammatory cytokines and chemokines via the human homolog MRGPRX2. Surprisingly, the SP-mediated inflammatory responses were independent of its canonical receptor, neurokinin-1 receptor (NK-1R). These results identify Mrgprb2/X2 as an important neuroimmune modulator and a potential target for treating inflammatory pain.

Original languageEnglish (US)
Pages (from-to)412-420.e3
JournalNeuron
Volume101
Issue number3
DOIs
StatePublished - Feb 6 2019

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Neurogenic Inflammation
Substance P
Mast Cells
Hyperalgesia
Chemokines
Pain
Cytokines
Neurokinin-1 Receptors
Nerve Endings
Neuropeptides
Peripheral Nerves
Cell Movement
Wounds and Injuries

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain. / Green, Dustin P.; Limjunyawong, Nathachit; Gour, Naina; Pundir, Priyanka; Dong, Xinzhong.

In: Neuron, Vol. 101, No. 3, 06.02.2019, p. 412-420.e3.

Research output: Contribution to journalArticle

Green, Dustin P. ; Limjunyawong, Nathachit ; Gour, Naina ; Pundir, Priyanka ; Dong, Xinzhong. / A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain. In: Neuron. 2019 ; Vol. 101, No. 3. pp. 412-420.e3.
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