Autonomous nervous system modulation by percutaneous auricular vagus nerve stimulation: Multiparametric assessment and implications for clinical use in diabetic foot ulcerations

Chronic diseases such as diabetes mellitus are usually associated with a dysregulation of autonomic state, i.e., an imbalanced sympathovagal activity. A reduced vagal tone promotes autonomic neuropathy, impaired microcirculatory perfusion and upregulated pro-inflammatory pathways. In case of peripheral tissue trauma this may lead to chronic foot ulcerations. As a counter measure, a targeted modulation of parasympathetic activity by percutaneous auricular vagus nerve stimulation may have beneficial effects on autonomic regulation in diabetics, and thus may improve wound condition. The present study reveals novel effects of this stimulation on autonomic modulation in healthy and diabetics, assessed by time and frequency domain measures of heart rate variability (HRV). Increased HRV in diabetics and healthy subjects in response to stimulation was observed (e.g., 101% and 57% increase in the median parasympathetic power, respectively). Modulation of total HRV, when corrected for changes in mean heart rate, differs significantly between both groups with more pronounced but delayed effects in diabetics. Presented results provide new evidence for potential beneficial effects of auricular vagus nerve stimulation on autonomic balance as a possible therapeutic approach in diabetic foot ulcerations.