Trigeminal nerve stimulation triggers oral mast cell activation and vascular permeability

Ann Allergy Asthma Immunol. 2014 Jan;112(1):40-5. doi: 10.1016/j.anai.2013.10.011. Epub 2013 Nov 9.


Background: The nervous system contributes to the pathophysiology of allergic and inflammatory diseases, including oral inflammation. Mast cells (MCs) are involved in their pathogenesis through proinflammatory mediator release.

Objective: To investigate the effect of trigeminal nerve (TN) stimulation compared with sham operation on MC activation and oral vascular permeability in the gingiva, palate, buccal mucosa, and tongue of the rat and to examine the possible role of substance P using rats treated with capsaicin as neonates to deplete substance P.

Methods: Six male Sprague-Dawley rats (250 g) were anesthetized and injected intravenously with Evans Blue (EB). Six other rats were injected neonatally with capsaicin (n = 3) or solvent (n = 3) and then injected with EB when they reached 250 g. The mandibular branch of the TN was stimulated for 1 minute (n = 3), and the remaining rats (n = 3) were subjected to sham operation. The ipsilateral and contralateral sides of the mouth were examined for EB extravasation, and tissue sections were removed for light and electron microscopy.

Results: TN stimulation resulted in EB extravasation in the ipsilateral side compared with the contralateral side or the ipsilateral side of sham-operated rats. Significant degranulation of MCs also was evident only on the ipsilateral side (P < .0001). There was no difference in MC degranulation between the vehicle- and capsaicin-treated rats, implying that neuropeptides other than substance P may be involved.

Conclusion: This is the first time that TN stimulation has been shown to result in MC activation and oral vascular permeability, suggesting that MC inhibitors may be used for the treatment of oral inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipruritics / pharmacology
  • Capillary Permeability / drug effects*
  • Capsaicin / pharmacology*
  • Evans Blue / pharmacology
  • Inflammation / immunology
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mouth / innervation
  • Mouth / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Substance P / metabolism
  • Transcutaneous Electric Nerve Stimulation*
  • Trigeminal Nerve / drug effects*


  • Antipruritics
  • Substance P
  • Evans Blue
  • Capsaicin