Analgesic Effects of Vagus Nerve Stimulation on Visceral Hypersensitivity: A Direct Comparison Between Invasive and Noninvasive Methods in Rats

Neuromodulation. 2023 May 15;S1094-7159(23)00153-8. doi: 10.1016/j.neurom.2023.04.001. Online ahead of print.


Objectives: The aims of this study were to investigate analgesic effects of vagus nerve stimulation (VNS) on visceral hypersensitivity (VH) in a rodent model of functional dyspepsia (FD) and to compare invasive VNS with noninvasive auricular VNS (aVNS).

Materials and methods: Eighteen ten-day-old male rats were gavaged with 0.1% iodoacetamide (IA) or 2% sucrose solution for six days. After eight weeks, IA-treated rats were implanted with electrodes for VNS or aVNS (n = 6 per group). Different parameters, varying in frequency and stimulation duty cycle, were tested to find the best parameter based on the improvement of VH assessed by electromyogram (EMG) during gastric distension.

Results: Compared with sucrose-treated rats, visceral sensitivity was increased significantly in IA-treated "FD" rats and ameliorated remarkably by VNS (at 40, 60, and 80 mm Hg; p ≤ 0.02, respectively) and aVNS (at 60 and 80 mm Hg; p ≤ 0.05, respectively) with the parameter of 100 Hz and 20% duty cycle. There was no significant difference in area under the curve of EMG responses between VNS and aVNS (at 60 and 80 mm Hg, both p > 0.05). Spectral analysis of heart rate variability revealed a significant enhancement in vagal efferent activity while applying VNS/aVNS compared with sham stimulation (p < 0.01). In the presence of atropine, no significant differences were noted in EMG after VNS/aVNS. Naloxone blocked the analgesic effects of VNS/aVNS.

Conclusions: VNS/aVNS with optimized parameter elicits ameliorative effects on VH, mediated by autonomic and opioid mechanisms. aVNS is as effective as direct VNS and has great potential for treating visceral pain in patients with FD.

Keywords: Functional gastrointestinal disorders; vagus nerve stimulation; visceral pain.