Figure 1.

(A) The vasomotor axon reflex: iontophoresis of acetylcholine results in stimulation of peripheral epidermal nociceptive C-fibers and thereafter indirectly results in local vasodilatation. The topical stimulation depolarizes unmyelinated C-fibers in the skin and results in afferent action potentials that are conducted orthodromically toward the spinal cord. At branching points of the nerve, the impulse continues antidromically, ending at arterial dermal vessels adjacent to the initial stimulation point. There, the axon reflex induces the release of vasoactive substances, such as substance P and calcitonin gene-related peptide, from nerve terminals and leads to vasodilation. (B) Laser Doppler imager setup and principle of measurement. (C) The upper panel shows the color-coded laser Doppler imaging perfusion data with iontophoresis probe framing direct vasodilation induced by direct stimulation as well as axon reflex-mediated enhancement of blood flow (“flare”) in an adjacent skin area surrounding the probe (“indirect flare”). The lower panel shows the extracted axon reflex flare, which provides a measure of functional integrity of those nociceptive C-fibers that mediate the vasomotor axon reflex upon activation through acetylcholine.