Development of an experimental model to study trigeminal nerve-mediated vasodilation on the human forehead

Cephalalgia. 2014 Jun;34(7):514-22. doi: 10.1177/0333102413517773. Epub 2014 Jan 3.


Background: During migraine, trigeminal sensory nerve terminals release calcitonin gene-related peptide (CGRP), inducing nociception and vasodilation. Applied on the skin, capsaicin activates the transient receptor potential vanilloid type 1 (TRPV1) channel and releases CGRP from sensory nerve terminals, thus increasing dermal blood flow (DBF). Using capsaicin application and electrical stimulation of the forehead skin, a trigeminal nerve-innervated dermatome, we aimed to develop a model to measure trigeminal nerve-mediated vasodilation in humans.

Methods: Using laser Doppler imaging, forehead DBF responses to application of capsaicin (0.06 mg/ml and 6.0 mg/ml) and saline, with and without iontophoresis, were studied in healthy subjects. The within-subject coefficient of variation (WCV) of repeated DBF measurements was calculated to assess reproducibility.

Results: Maximal DBF responses to 6.0 mg/ml capsaicin with and without iontophoresis did not differ (Emax 459 ± 32 and 424 ± 32 arbitrary units (a.u.), WCV 6 ± 4%). In contrast, DBF responses to 0.06 mg/ml capsaicin were significantly larger with than without iontophoresis (Emax 307 ± 60 versus 187 ± 21 a.u., WCV 21 ± 13%). Saline with iontophoresis significantly increased DBF (Emax: 245 ± 26 a.u, WCV 11 ± 8%), while saline application without iontophoresis did not affect DBF.

Conclusion: Topical application of capsaicin and electrical stimulation induce reproducible forehead DBF increases and therefore are suitable to study trigeminal nerve-mediated vasodilation in humans.

Keywords: CGRP; Capsaicin; electrical stimulation; iontophoresis; laser Doppler; trigeminal nerve-mediated vasodilation.

MeSH terms

  • Administration, Topical
  • Adult
  • Calcitonin Gene-Related Peptide / physiology*
  • Capsaicin / pharmacology
  • Female
  • Forehead / blood supply*
  • Forehead / innervation*
  • Humans
  • Iontophoresis
  • Laser-Doppler Flowmetry
  • Male
  • Migraine Disorders / physiopathology*
  • Nociception / physiology
  • Skin / blood supply
  • Skin / innervation
  • Trigeminal Nerve / physiology*
  • Vasodilation / physiology*


  • Calcitonin Gene-Related Peptide
  • Capsaicin