Differential Involvement Of Myelinated And Unmyelinated Nerve Fibers In Painful Diabetic Polyneuropathy

Background We aimed at evaluating the differential involvement of large myelinated A beta-, small myelinated A delta-, and unmyelinated C-fibers in patients with diabetic polyneuropathy and how they contribute to neuropathic pain.Methods We collected clinical and diagnostic test variables in 133 consecutive patients with diabetic polyneuropathy. All patients underwent A beta-fiber mediated nerve conduction study, A delta-fiber mediated laser-evoked potentials and skin biopsy mainly assessing unmyelinated C-fibers.Results Pure 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.Conclusions Diabetic polyneuropathy mainly manifests as a mixed-fiber polyneuropathy, simultaneously involving A beta-, A delta-, 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.