Abstract
Background: The autonomic nervous system (ANS) is fundamental to maintaining our bodies physiological state, regulating functions such as heart rate, gastrointestinal function, and the immune system. Recent evidence highlights the immunomodulatory effect of parasympathetic nervous system on systemic inflammation due to it’s role in the cholinergic anti-inflammatory pathway. Vagal nerve stimulation (VNS) engages this network, evoking an anti-inflammatory effect through this pathway. However, the invasive nature of VNS hinders it’s therapeutic opportunity, ultimately constraining it’s potential to benefit patients. This has prompted exploration into non-invasive approaches to tap into this network. Existing non-invasive approaches remain visible, whereas a subtle option would enhance patient comfort. Invasive stimulation of the deep peroneal nerve (DPN) has shown to leverage efferent vagal signalling and activate this cholinergic anti-inflammatory pathway. This study aimed to investigate whether non-invasive stimulation of the DPN could result in similar modulation of the parasympathetic nervous system.
Methods: This randomized, crossover study recruited 24 healthy adult participants. Transcutaneous electric nerve stimulation (TENS) was delivered to the cutaneous distribution of the DPN, located on the dorsum of the foot. Each participant attended three stimulation sessions in a randomised order, high-frequency (80 Hz), low-frequency (10 Hz), and placebo. Time domain heart rate variability (HRV) parameters, recorded by an electrocardiogram (ECG), were used to evaluate the effect of the TENS on the ANS activity. The root mean square of successive differences (RMSSD) served as an index of parasympathetic activity, whereas stress index (SI) reflected sympathetic activity.
Results: Paired t-test analysis revealed a statistically significant difference between baseline and the 10-minute post-stimulation period for RMSSD in the high frequency group (p = 0.0284), but not in low frequency or placebo groups. A significant difference was observed in RMSSD for the 0-5-minute post-stimulation interval following high frequency stimulation (p = 0.0393), but not in the 5-10-minute post-stimulation period. This suggests that the effect may be transient and diminish over time. Although previous studies have shown that stimulation amplitude can influence post-stimulation outcome, this study found no correlation between stimulation intensity and HRV.
Conclusion: Overall this study demonstrates, for the first time, promising outcomes of non-invasive DPN stimulation on parasympathetic activity. Due to the small sample size, future larger scale studies are needed to validate these findings and provide greater insight into it’s effects.