title: Sensory nerves contribute to cutaneous vasodilator response to cathodal stimulation in healthy rats.
abstract: Cutaneous current-induced vasodilation (CIV) in response to galvanic current application is an integrative model of neurovascular interaction that relies on capsaicin-sensitive fiber activation. The upstream and downstream mechanisms related to the activation of the capsaicin-sensitive fibers involved in CIV are not elucidated. In particular, the activation of cutaneous transient receptor potential vanilloid type-1 (TRPV1) channels and/or acid-sensing ion channels (ASIC) (activators mechanisms) and the release of calcitonin gene-related peptide (CGRP) and substance P (SP) (effector mechanisms) have been tested. To assess cathodal CIV, we measured cutaneous blood flow using laser Doppler flowmetry for 20min following cathodal current application (240s, 100μA) on the skin of the thigh in anesthetized healthy rats for 20min. CIV was studied in rats treated with capsazepine and amiloride to inhibit TRPV1 and ASIC channels, respectively; CGRP8-37 and SR140333 to antagonize CGRP and neurokinin-1 (NK1) receptors, respectively; compared to their respective controls. Cathodal CIV was attenuated by capsazepine (12±2% vs 54±6%, P<0.001), amiloride (19±8% vs 61±6%, P<0.01), CGRP8-37 (15±6% vs 61±6%, P<0.001) and SR140333 (9±5% vs 54±6%, P<0.001) without changing local acidification. This is the first integrative study performed in healthy rats showing that cutaneous vasodilation in response to cathodal stimulation is initiated by activation of cutaneous TRPV1 and ASIC channels likely through local acidification. The involvement of CGRP and NK1 receptors suggests that cathodal CIV is the result of CGRP and SP released through activated capsaicin-sensitive fibers. Therefore cathodal CIV could be a valuable method to assess sensory neurovascular function in the skin, which would be particularly relevant to evaluate the presence of small nerve fiber disorders and the effectiveness of treatments.
authors.affiliation: Department of Comparative and Biomedical Sciences, Royal Veterinary College, London NW1 0TU, United Kingdom.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gohin
authors.affiliation: Laboratory of Tissue Biology and Therapeutic Engineering UMR5305 University of Lyon 1 and Centre National de la Recherche Scientifique (CNRS) IBCP, 7 passage du vercors 69367 Lyon cedex France; University of Lyon 1, UMR 5305, Lyon, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Decorps
authors.affiliation: Laboratory of Tissue Biology and Therapeutic Engineering UMR5305 University of Lyon 1 and Centre National de la Recherche Scientifique (CNRS) IBCP, 7 passage du vercors 69367 Lyon cedex France; University of Lyon 1, UMR 5305, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sigaudo-Roussel
authors.affiliation: Laboratory of Tissue Biology and Therapeutic Engineering UMR5305 University of Lyon 1 and Centre National de la Recherche Scientifique (CNRS) IBCP, 7 passage du vercors 69367 Lyon cedex France; University of Lyon 1, UMR 5305, Lyon, France. Electronic address: berengere.fromy@univ-lyon1.fr.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Fromy
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000584:Amiloride / Q000737:chemistry; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000737:chemistry; D004566:Electrodes; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D010446:Peptide Fragments / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011812:Quinuclidines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000473:pathology*; D012867:Skin / Q000098:blood supply / Q000473:pathology*; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); C085215:SR 140333; D013373:Substance P; D000584:Amiloride; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin
keywords: Cutaneous afferent; Electrical stimulation; Microcirculation; Neurovascular interaction; Sensory fibers