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

Background The vagus nerve exerts an anti-nociceptive effect in the viscera. Aims To investigate whether transcutaneous vagal nerve stimulation (t-VNS) prevents the development 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.