Transcutaneous vagus nerve stimulation prevents the development of, and reverses, established oesophageal pain hypersensitivity

Aliment Pharmacol Ther. 2020 Sep;52(6):988-996. doi: 10.1111/apt.15869. Epub 2020 Aug 7.

Abstract

Background: The vagus nerve exerts an anti-nociceptive effect on the viscera.

Aim: To investigate whether transcutaneous vagal nerve stimulation (t-VNS) prevents the development of and/or reverses established visceral hypersensitivity in a validated model of acid-induced oesophageal pain.

Methods: Before and after a 30-minute infusion of 0.15M hydrochloric acid into the distal oesophagus, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus. Validated sympathetic (cardiac sympathetic index) and parasympathetic (cardiac vagal tone [CVT]) nervous system measures were recorded. In study 1, 15 healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham for 30 minutes during acid infusion. In study 2, 18 different healthy participants were randomised in a blinded crossover design to receive either t-VNS or sham, for 30 minutes after acid infusion.

Results: Study 1: t-VNS increased CVT (31.6% ± 58.7 vs -9.6 ± 20.6, P = 0.02) in comparison to sham with no effect on cardiac sympathetic index. The development of acid-induced oesophageal hypersensitivity was prevented with t-VNS in comparison to sham (15.5 mA per unit time (95% CI 4.9 - 26.2), P = 0.004). Study 2: t-VNS increased CVT (26.3% ± 32.7 vs 3 ± 27.1, P = 0.03) in comparison to sham with no effect on cardiac sympathetic index. t-VNS reversed established acid-induced oesophageal hypersensitivity in comparison to sham (17.3mA/unit time (95% CI 9.8-24.7), P = 0.0001).

Conclusions: t-VNS prevents the development of, and reverses established, acid-induced oesophageal hypersensitivity. These results have therapeutic implications for the management of visceral pain hypersensitivity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Esophagus / pathology
  • Female
  • Humans
  • Hyperalgesia / prevention & control*
  • Male
  • Middle Aged
  • Pain / prevention & control*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Transcutaneous Electric Nerve Stimulation / methods*
  • Vagus Nerve / physiology
  • Vagus Nerve Stimulation / methods*
  • Young Adult