Induction of vascular endothelial growth factor release by transcutaneous frequency modulated neural stimulation in diabetic polyneuropathy

Background: Pharmacological treatment for diabetic polyneuropathy (DP) has shown limited benefit; frequency-modulated electrical stimulation (FREMS) has shown positive results in pain control and nerve conduction velocity in DP. Objective: To investigate the effects of FREMS vs transcutaneous electrical nerve stimulation (TENS) on the release of vascular endothelial growth factor (VEGF) in Type 2 diabetic and in non-diabetic subjects. Methods: 10 non-diabetic [mean age 37±5 yr; females (F)/males (M): 6/4] and 10 Type 2 diabetic subjects (mean age 52±6 yr; F/M: 5/5) with DP underwent TENS (for 10 min) followed by 30 min interval without electrical stimulation, and then FREMS (for 10 min) over the forearm volar surface. Blood samples for VEGF measurements were obtained from the contra-lateral arm every 2 min during TENS/FREMS application and every 10 min during the intervals. Results: We observed a significant rise in plasma VEGF during FREMS in both non-diabetic and diabetic subjects (maximal response 89.4±80.3 pg/ml and 48.5±18.3 pg/ml, respectively; p<0.01 vs basal) with a lower, but still significant response in diabetics. No changes in VEGF were observed during TENS application. Conclusion: VEGF release during FREMS may help explain the positive effects on nerve conduction velocity in DP, possibly mediated by favorable effects on vasa nervorum microangiopathy.