Sural nerve fibre pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology

Nerve fibre pathology is poorly described in diabetic patients with mild neuropathy and has not been adequately related to clinical evaluation, quantitative sensory examination and neurophysiology. Sural nerve myelinated and unmyelinated fibre pathology was morphometrically quantified and related to the presence of pain and conventional measures of neuropathic severity in 15 diabetic patients with mild neuropathy and 14 control subjects. Diabetic patients demonstrated a significant (P<0.01) reduction in myelinated fibre density, but no change in fibre/axonal area, or g-ratio, compared to control subjects. Unmyelinated fibre degeneration was evidenced by an increase in the percentage of unassociated Schwann cell profiles (P<0.0001) and a reduction in axon density (P<0.0008) in diabetic patients. This was associated with a significant reduction in unmyelinated axon diameter (P<0.001) with a shift of the size frequency distribution to the left (P<0.02). Neurophysiology, quantitative sensory testing and nerve fibre pathology failed to differentiate diabetic patients with painful and painless neuropathy and failed to correlate with any measure of unmyelinated fibre pathology.