Density of sympathetic axons in sural nerve biopsies of neuropathy patients is related to painfulness

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Abstract
In this study, differences of unmyelinated nerve fiber density in sural nerve biopsy material from patients suffering from neuropathies of unknown origin with (n=14) or without pain (n=13) were analyzed. Immunocytochemistry was applied to differentiate afferent sensory and efferent sympathetic nerve fibers. All patients were evaluated for deficits of small fiber function with thermotesting, quantitative sudomotor-axon reflex-testing and testing of painfulness of mechanical stimuli before performing the biopsy. No difference was found between patients with and without pain concerning clinical deficits or results in any of the neurophysiological examinations. There were also no histopathological differences concerning the density of afferent C-fibers. However, absolute and relative density of efferent sympathetic nerve fibers was significantly higher in patients with painful neuropathy (P<0.001), although none of the patients demonstrated clinical sympathetic abnormalities. We conclude that an imbalance between afferent and sympathetic nerve fiber density in the periphery may contribute to neuropathic pain even in those patients without obvious clinical autonomic disturbances.