Clinical application of respiratory-gated auricular vagal afferent nerve stimulation

Vagus nerve stimulation (VNS) has garnered significant attention as a promising bioelectronic therapy. In recent years, respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), a novel non-invasive vagus nerve stimulation technique, has emerged. RAVANS integrates respiration with transcutaneous auricular vagus nerve stimulation (taVNS) and shares a similar mechanism of action to traditional VNS. Similar to conventional Vagus Nerve Stimulation (VNS), RAVANS may mitigate brain injury through three primary pathways: reducing neuronal apoptosis, modulating neurotransmitter release, and influencing inflammatory factor pathways. In this paper, we emphasize how RAVANS enhances the activation of nucleus of the solitary tract （NTS）and the locus coeruleus by regulating the monoaminergic and GABA systems through respiratory control. Additionally, it leverages the beneficial effects of respiration on the central nervous system. In this review, we delineate the potential mechanisms of action of RAVANS, provide a comprehensive overview of its clinical applications in chronic low back pain, migraine, depression, hypertension, and cognitive disorders. Furthermore, we offer future perspectives on optimizing the parameters of RAVANS and its application in post-stroke dysphagia. This will pave the way for new avenues in RAVANS research.