• Eleonora Galosi, Giuseppe Di Pietro, Silvia La Cesa, Giulia Di Stefano, Caterina Leone, Alessandra Fasolino, Andrea Di Lionardo, Frida Leonetti, Raffaella Buzzetti, Cristina Mollica, Giorgio Cruccu, and Andrea Truini.
• Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
• Muscle Nerve. 2021 Jan 1; 63 (1): 68-74.

BackgroundWe aimed at evaluating the differential involvement of large myelinated Aβ-, small myelinated Aδ-, and unmyelinated C-fibers in patients with diabetic polyneuropathy and how they contribute to neuropathic pain.MethodsWe collected clinical and diagnostic test variables in 133 consecutive patients with diabetic polyneuropathy. All patients underwent Aβ-fiber mediated nerve conduction study, Aδ-fiber mediated laser-evoked potentials and skin biopsy mainly assessing unmyelinated C-fibers.ResultsPure large-fiber and small-fiber polyneuropathy were relatively uncommon; conversely mixed-fiber polyneuropathy was the most common type of diabetic polyneuropathy (74%). The frequency of neuropathic pain was similar in the three different polyneuropathies. Ongoing burning pain and dynamic mechanical allodynia were similarly associated with specific small-fiber related variables.ConclusionsDiabetic polyneuropathy mainly manifests as a mixed-fiber polyneuropathy, simultaneously involving Aβ-, Aδ-, and C-fibers. In most patients, neuropathic pain is distinctly associated with small-fiber damage. The evidence that the frequency of neuropathic pain does not differ across pure large-, pure small-, and mixed-fiber polyneuropathy, raises the possibility that in patients with pure large-fiber polyneuropathy nociceptive nerve terminal involvement might be undetected by standard diagnostic techniques.© 2020 Wiley Periodicals LLC.

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