The Effect of Transcutaneous Vagal Nerve Stimulation on Reducing Oesophageal Pain Hypersensitivity

Chronic oesophageal pain is a symptomatic feature of disorders such as erosive oesophagitis, non-erosive reflux disease and non-cardiac chest pain. Patients often display heightened sensitivity to intra-oesophageal stimuli, which is referred to as oesophageal pain hypersensitivity. However, the experience of oesophageal pain is highly individual with a multitude of factors proposed to account for this variability. Amongst the physiological factors is the autonomic nervous system (ANS). The ANS has been postulated to play a pivotal role in the modulation of pain through its multiple interactions with pain processing. The ANS has two broadly antithetic branches, the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS). The primary neural substrate of the PNS is the vagus nerve. The vagus nerve is increasingly considered to play an integral role in modulating oesophageal pain. Electrical vagal nerve stimulation (VNS) was first used in humans in 1988 and is an efficacious treatment for drug resistant epilepsy. Traditional VNS is undertaken in a procedure where a bipolar helical electrode is placed around the cervical vagal nerve, which is connected to a pulse generator placed in subcutaneous pocket in the chest, not dissimilar to a cardiac pacemaker. However, this method of VNS necessitates surgical implantation with its attendant risks and complications. Recently, an external transcutaneous VNS (t-VNS) system, consisting of an earplug-like electrode to interface with the concha of the outer ear and a handheld battery-powered electrical stimulator, has become commercially available (NEMOS system). The auricular branch of the vagus nerve innervates the concha of the ear and is located directly under the skin, making it a suitable target for transcutaneous stimulation. t-VNS has been demonstrated to be safe, well tolerated and have a high degree of user-friendliness. A preliminary study has reported that t-VNS reduces sensitivity to heat pain in healthy volunteers. Furthermore, recent studies have demonstrated that t-VNS patterns of cerebral activation, as determined by functional magnetic resonance imaging, were similar to those evoked by traditional VNS. Thus, VNS per se represents an attractive proposition for investigating the role of the PNS in oesophageal pain and t-VNS specifically, a viable, safe and acceptable technology for achieving this. The pivotal experiments evaluating the analgesic role of VNS in the development of acid induced oesophageal pain hypersensitivity have not been conducted. Using the aforementioned model of oesophageal pain hypersensitivity, we seek to determine the analgesic effect of t-VNS.