Small-fibre involvement in diabetic patients with neuropathic foot pain

Aims To assess small-fibre involvement in diabetic patients with neuropathic pain. Methods Peripheral nerve function was assessed in 30 patients with Type 2 diabetes mellitus (T2DM, n = 24) or impaired glucose tolerance (IGT, n = 6), and clinical symptoms of neuropathic pain in the feet, using nerve conduction studies, autonomic tests, thermal quantitative sensory testing (T-QST) and quantification of intra- and subepidermal nerve fibre densities in skin punch biopsies. Results Clinical signs of isolated small-fibre sensory involvement were present in 13 patients [pure small-fibre neuropathy (pSFN)], seven patients had isolated positive sensory symptoms without neurological deficits (pSFN-). Ten patients had concomitant electrophysiological and/or clinical signs of large-fibre sensory involvement [mixed-fibre neuropathy (MFN)]. Twenty-seven patients (90%) had both reduced skin innervation and abnormalities of the T-QST parameters. Two other patients displayed either abnormal skin innervation or T-QST, and only one patient had normal findings on both tests. The criteria of small-fibre neuropathy (SFN) were met in all 20 patients without large-fibre involvement. Small-fibre involvement was also present in the 10 MFN patients. Both T-QST and skin biopsy parameters revealed significant differences between these clinical subgroups, with increased severity of small-fibre involvement in the MFN group. Autonomic dysfunction was found in 43% of patients and did not correlate with either clinical, T-QST or skin biopsy data. Conclusions Although the exact mechanism of neuropathic pain in diabetic patients is not known, pain is almost invariably accompanied by small-fibre dysfunction and pathology irrespective of autonomic or large-fibre involvement.