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 journalArticlepeer-review

226 Scopus citations


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
Issue number3
StatePublished - Feb 6 2019
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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