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

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 (E-max 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 (E-max 307 +/- 60 versus 187 +/- 21 a.u., WCV 21 +/- 13%). Saline with iontophoresis significantly increased DBF (E-max: 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.