title: Development of an experimental model to study trigeminal nerve-mediated vasodilation on the human forehead.
abstract: 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.
  
  
  CONCLUSIONS
  Topical application of capsaicin and electrical stimulation induce reproducible forehead DBF increases and therefore are suitable to study trigeminal nerve-mediated vasodilation in humans.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Ibrahimi
authors.affiliation: Center for Clinical Pharmacology, University Hospital Gasthuisberg (KU Leuven), Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Vermeersch
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, the Netherlands.
authors.forename: Ahj
authors.initials: A
authors.lastname: Danser
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México.
authors.forename: C M
authors.initials: CM
authors.lastname: Villalón
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, the Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: Center for Clinical Pharmacology, University Hospital Gasthuisberg (KU Leuven), Belgium.
authors.forename: J
authors.initials: J
authors.lastname: de Hoon
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, the Netherlands a.vanharen-maassenvandenbrink@erasmusmc.nl.
authors.forename: A
authors.initials: A
authors.lastname: MaassenVanDenBrink
mesh_terms: D000287:Administration, Topical; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005546:Forehead / Q000098:blood supply* / Q000294:innervation*; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology*; D059225:Nociception / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000294:innervation; D014276:Trigeminal Nerve / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin
keywords: CGRP; Capsaicin; electrical stimulation; iontophoresis; laser Doppler; trigeminal nerve-mediated vasodilation