Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice

Kristiana Kandere-Grzybowska, Daniela Gheorghe, Josef Priller, Pamela Esposito, Man Huang, Norma Gerard, Theoharis C Theoharides

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Migraine headaches are often precipitated by stress and seem to involve neurogenic inflammation (NI) of the dura mater associated with the sensation of throbbing pain. Trigeminal nerve stimulation had been reported to activate rat dura mast cells and increase vascular permeability, effects inhibited by neonatal pretreatment with capsaicin implicating sensory neuropeptides, such as substance P (SP). The aim of the present study was to investigate NI, assessed by extravasation of 99-Technetium-gluceptate (99Tc-G), as well as the role of mast cells, SP and its receptor (NK-1R) in dura mater of mice in response to acute stress. Restraint stress for thirty min significantly increased 99Tc-G extravasation in the dura mater of C57BL mice. This effect was absent in W/W(v) mast cell-deficient mice and NK-1 receptor knockout mice (NK-1R-/-), but was unaltered in SP knockout mice (SP-/-). Acute restraint stress also resulted in increased dura mast cell activation in C57BL mice, but not in NK-1R-/- mice. These data demonstrate for the first time that acute stress triggers NI and mast cell activation in mouse dura mater through the activation of NK-1 receptors. The fact that SP-/- mice had intact vascular permeability response to stress indicates that some other NK-1 receptor agonist may substitute for SP. These results may help explain initial events in pathogenesis of stress-induced migraines.

Original languageEnglish
Pages (from-to)213-20
Number of pages8
JournalBrain Research
Issue number2
Publication statusPublished - 8 Aug 2003

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Capillary Permeability
  • Corticosterone
  • Dura Mater
  • Female
  • Male
  • Mast Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Neurokinin-1
  • Stress, Physiological
  • Comparative Study
  • Journal Article
  • Research Support, U.S. Gov't, P.H.S.


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