Abstract
Cutaneous autonomic small nerve fibers encompass unmyelinated C-fibers and thinly myelinated Aδ-fibers, which innervate dermal vessels (vasomotor fibers), sweat glands (sudomotor fibers), and hair follicles (pilomotor fibers). Analysis of their integrity can capture early pathology in autonomic neuropathies such as diabetic autonomic neuropathy or peripheral nerve inflammation due to infectious and autoimmune diseases. Furthermore, intraneural deposition of alpha-synuclein in synucleinopathies such as Parkinson’s disease can lead to small fiber damage. Research indicated that detection and quantitative analysis of small fiber pathology might facilitate early diagnosis and initiation of treatment. While autonomic neuropathies show substantial etiopathogenetic heterogeneity, they have in common impaired functional integrity of small nerve fibers. This impairment can be evaluated by quantitative analysis of axonal responses to iontophoretic application of adrenergic or cholinergic agonists to the skin. The axon-reflex can be elicited in cholinergic sudomotor fibers to induce sweating and in cholinergic vasomotor fibers to induce vasodilation. Currently, only few techniques are available to quantify axon-reflex responses, the majority of which is limited by technical demands or lack of validated analysis protocols. Function of vasomotor small fibers can be analyzed using laser Doppler flowmetry, laser Doppler imaging, and laser speckle contrast imaging. Sudomotor function can be assessed using quantitative sudomotor axon-reflex test, silicone imprints, and quantitative direct and indirect testing of sudomotor function. More recent advancements include analysis of piloerection (goose bumps) following stimulation of adrenergic small fibers using pilomotor axon-reflex test. We provide a review of the current literature on axon-reflex tests in cutaneous autonomic small fibers.
Highlights
Autonomic small fibers mediate neural control of vital organs such as the cardiovascular, bronchopulmonary, gastrointestinal, and urogenital system as well as the skin
Autonomic neuropathies comprise a group of etiopathogenetically heterogenous disorders, which can manifest with vegetative symptoms such as orthostatic hypotension, reduced heart rate variability, sexual and urogenital dysfunction, and dyshidrosis of the skin, frequently reducing quality of life [1, 2]
Autonomic neuropathies are of high clinical relevance. This is further highlighted by an increase of mortality in those autonomic neuropathies that impair neural control of the cardiovascular system [3]
Summary
Autonomic small fibers mediate neural control of vital organs such as the cardiovascular, bronchopulmonary, gastrointestinal, and urogenital system as well as the skin. Autonomic neuropathies are defined by damage to lightly myelinated A-delta and unmyelinated C-fibers. These “small fibers” constitute the most peripheral segments of the sympathetic and parasympathetic branch of the autonomic nervous system. Autonomic neuropathies are of high clinical relevance This is further highlighted by an increase of mortality in those autonomic neuropathies that impair neural control of the cardiovascular system [3]. Neurol Sci (2020) 41:1685–1696 autonomic neuropathy can be associated with infectious diseases such as acquired immune deficiency syndrome, hereditary disorders such as Fabry disease, channelopathies, hereditary sensory, and autonomic neuropathies as well as neurotoxins such as Shiga toxin or cisplatin [4].
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