Electrically stimulated axon reflexes are diminished in diabetic small fiber neuropathies

Axon reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic axon reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, electrical thresholds for flare induction were increased (thighs P < 0.001 and feet P < 0.03). In NO-Ns, flare size at the feet (P < 0.02) and flux at both sites (thighs P < 0.001 and feet P < 0.002) were even increased. Test/retest evaluation of our method revealed a good correlation (r = 0.83, P < 0.004). Intracutaneous electrical stimulation of C-fibers and scanning the flare with LDI is a sensitive tool to reliably detect small fiber impairment in diabetic SFN subjects and even increased neuropeptide release in NO-Ns.