title: No alpha-adrenoreceptor-induced C-fiber activation in healthy human skin.
abstract: In healthy volunteers, flare responses induced by norepinephrine (NE) iontophoresis have been observed. However, as NE iontophoresis is a combined electrical and chemical stimulus axon, reflexes cannot be directly linked to pharmocological activity of NE. Different concentrations of NE, clonidine (CL), and phenylephrine (PE) (NE: 10(-10)-10(-3) M; CL and PE: 10(-8)-10(-3) M) were applied via intradermal microdialysis fibers into the skin of healthy volunteers. Simultaneously, skin blood flow was visualized by laser-Doppler imaging scans and quantified in a vasoconstriction skin area directly above the membranes to control drug effects and in expected axon reflex vasodilation areas that were 0.75 cm apart. NE, PE, and CL caused dose-dependent vasoconstriction. However, neither in the presumed axon reflex areas (quantitative analysis) nor on laser-Doppler imaging pictures (qualitative analysis) were any vasodilation observed. Even at concentrations causing maximum vasoconstriction (10(-3) M for any drug), no vasodilation was induced. Our results indicate that, in healthy human skin, exogenously supplied alpha-adrenoreceptor agonists alone do not activate nociceptors sufficiently to induce axon reflex flare.
authors.affiliation: Department of Neurology, Friedrich Alexander Universität Erlangen, Erlangen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zahn
authors.forename: Stefan
authors.initials: S
authors.lastname: Leis
authors.forename: Christoph
authors.initials: C
authors.lastname: Schick
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Frank
authors.initials: F
authors.lastname: Birklein
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001369:Axons / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012016:Reference Values; D012018:Reflex / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000294:innervation*; D014661:Vasoconstriction
chemical_list: D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003000:Clonidine; D009638:Norepinephrine