No alpha-adrenoreceptor-induced C-fiber activation in healthy human skin

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.