In the last decade, skin biopsy has enhanced the diagnostic armamentarium in peripheral neuropathies with the opportunity to easily investigate small diameter sensory nerves, in particular somatic unmyelinated fibres. There is no neurophysiological test for the routine examination of this class of nerve fibres. Moreover, although quantitative sensory testing – psychophysical thresholds for warm, cold, and heat pain that are functions of unmyelinated C and small myelinated Aσ fibres – may be useful in population studies, they are of no help diagnosing neuropathy in individual patients (Shy et al. 2003).
The presence of axons within the human epidermis was denied for more than a century by most investigators, despite Paul Langerhans’s first description in 1868 and further studies confirming his original work. This was due to the relative insensitivity of the staining methods, and to the lack of techniques to prevent derangement of skin nerve fibres which are so easily damaged during
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