title: Evidence for a vasomotor cyclo-oxygenase dependent mechanism of sensitization at the cutaneous level.
abstract: OBJECTIVE
  Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake.
  
  
  METHODS
  Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline.
  
  
  RESULTS
  Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days.
  
  
  CONCLUSIONS
  This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.
authors.affiliation: Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI) - Unité mixte UMR CNRS 6214 / INSERM U 1083, Faculté de Médecine, Angers, France.|Laboratory of Vascular Investigations, University Hospital of Angers, France.|CHU Rennes, Imagerie cœur-vaisseaux, F-35033, Rennes, France.|INSERM, Clinical Investigation Center CIC 1414, F-34043, Rennes, France.|Université de Rennes 1, F-34043, Rennes, France.
authors.forename: G
authors.initials: G
authors.lastname: Mahé
authors.affiliation: Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI) - Unité mixte UMR CNRS 6214 / INSERM U 1083, Faculté de Médecine, Angers, France.|Laboratory of Vascular Investigations, University Hospital of Angers, France.
authors.forename: P
authors.initials: P
authors.lastname: Abraham
authors.affiliation: LARIS - Laboratoire Angevin de Recherche en Ingénierie des Systèmes, Université d'Angers, 62 avenue Notre-Dame du Lac, 49000, Angers, France.
authors.forename: A
authors.initials: A
authors.lastname: Humeau-Heurtier
authors.affiliation: Laboratory of Vascular Investigations, University Hospital of Angers, France.
authors.forename: L
authors.initials: L
authors.lastname: Gascoin
authors.affiliation: Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI) - Unité mixte UMR CNRS 6214 / INSERM U 1083, Faculté de Médecine, Angers, France.|Laboratory of Vascular Investigations, University Hospital of Angers, France.
authors.forename: G
authors.initials: G
authors.lastname: Lefthériotis
authors.affiliation: Université du Maine, EA 4334, Motricité, Interactions, Performance, LUNAM Université, Le Mans, 72085, Cedex 9, France.
authors.forename: S
authors.identifier: http://orcid.org/0000-0003-1268-1694
authors.initials: S
authors.lastname: Durand
mesh_terms: D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007478:Iontophoresis / Q000009:adverse effects / Q000379:methods; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D012879:Skin Physiological Phenomena / Q000187:drug effects; D012881:Skin Temperature; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
chemical_list: D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin
keywords: blood flow; iontophoresis; laser Doppler flowmetry; prostaglandins; skin