Brain Effect of Vagal Nerve Stimulation at Rest and Pain

Plain-language summary

Pain is a ubiquitous distressing sensory experience and is the most frequent symptom in numerous gastrointestinal disorders including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Visceral pain is especially difficult to treat with conventional medications and new treatments are needed. Recently, the relationship between autonomic nerve system (ANS) and pain has gathered attention because it could represent an effective treatment target for visceral pain. The parasympathetic nervous system (PNS), one of the two main branches of the ANS, is considered to play an important role for analgesia possibly due to vagal nerve-mediated activation of key brain areas implicated in descending analgesia of pain. Transcutaneous vagal nerve stimulation (tVNS) can non-invasively modulate vagal nerve and be expected as a new method to treat visceral pain. For example, the preliminary study showed that vagal nerve stimulation experimentally modulated cardiac vagal tone (CVT) and prevented the development of acid-induced oesophageal hyperalgesia. Disturbances in ANS function have been reported not only in IBS patients but also in fibromyalgia and chronic pelvic pain syndrome. Many of these disorders have been associated with differences in brain structure and/or function as demonstrated by the use of structural and functional magnetic resonance imaging (fMRI). Of note, the investigators have recently shown that these differences in brain structure and function may be in part attributable to the aforementioned disturbance in ANS function, adding weight to the proposition that autonomic neuromodulation may be efficacious in pain disorders. For instance, in healthy participants the investigators have recently shown, using functional connectivity analysis, that higher resting parasympathetic CVT predicts the engagement of a subcortical functional network that is implicated in descending analgesia, thereby supporting the notion that vagal-mediated analgesia is achieved via descending inhibitory pathways1,4. Thus, tVNS seems a reasonable method to treat pain. However, to date, the precise real-time effect of tVNS on brain function, including during the processing of visceral pain is unknown. Hence, the aims of this study are to investigate the real-time effect of tVNS compared to sham stimulus on brain activity whilst experiencing acute oesophageal pain, using fMRI in double-blind, randomised crossover study of tVNS vs sham stimulation in healthy subjects.

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