Current Directions in the Auricular Vagus Nerve Stimulation I – A Physiological Perspective

Abstract

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects – a discussion of engineering aspects is provided by our accompanying article ( Kaniusas et al., 2019 ). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model

“…For atVNS condition, electrodes were placed in the concha of the left ear ( Fig. 1B) to avoid cardiac complications, as the right branch of the vagus nerve innervates the sinoatrial node and can have undesirable effects on heart rate [12]. For sham condition, electrodes were placed on the helix of the left auricle, outside of the ABVN innervated area.…”

Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation

“…Towards identifying potential biomarkers, recent basic research efforts have focused on gaining a more thorough understanding of the physiological mechanisms supporting clinical taVNS outcomes (as reviewed in Kaniusas et al [19,20]). For instance, non-invasive human neuroimaging using functional magnetic resonance imaging (fMRI) has been applied to assess brainstem response to taVNS in the nucleus tractus solitarii (NTS), a thin longitudinal nucleus located in the dorsal medulla, and the primary synapse for vagal afference [7,21e27].…”

Auricular neural stimulation as a new non-invasive treatment for opioid detoxification

“…Targeted neuromodulation through implanted and non-invasive devices is a core aspect of bioelectronic medicine (Pavlov et al 2019;Addorisio et al 2019). In addition to chronic inflammatory diseases, bioelectronic medicine has the potential to provide new treatments for many disorders and neuropsychiatric conditions, including chronic migraine, epilepsy, major depressive disorder, Alzheimer's disease, rheumatoid arthritis, pre-diabetes, paralysis, gastrointestinal diseases, and even cancer (Pavlov and Tracey 2017;Miller et al 2019;Kaniusas et al 2019;Eberhardson et al 2019). Among all the available bioelectronic neuromodulatory approaches, auricular vagus nerve stimulation (aVNS) has been increasingly utilized because of its low cost, ease of application, and because it is non-invasive (Pavlov et al 2019;Addorisio et al 2019).…”

“…The effects of neural stimulation for the treatment of neuropsychiatric diseases, using taVNS or percutaneous auricular stimulation as used in the recently FDA approved devices, appear to be very similar to auricular acupuncture which has been widely used for substance use disorders (Chen et al 2018;Baker and Chang 2016;Litscher 2019). Acupuncture has been shown to be effective for treating opioid withdrawal (Kaniusas et al 2019;Mercante et al 2018a;Mercante et al 2018b;Chen et al 2018). Studies indicate that acupuncture and electrical stimulation were more effective than medication and had fewer side effects such as insomnia, pain, and anxiety when used for treating withdrawal syndromes from acute discontinuation of opioids (Liu et al 2009).…”

“…For example, electro-acupuncture has been shown to reduce withdrawal behaviors in mice following abrupt discontinuation of morphine (Cheng et al 1980) and to suppress naloxone-induced morphine withdrawal in rats (Fung et al 1980). While the mechanisms of the widely used auricular acupuncture protocol are not fully understood, it is suggested that it works, at least in part, through regulation of the autonomic nervous system and immune responses (Kaniusas et al 2019;Mercante et al 2018b). Acupuncture needs to be administered by medical providers who have undergone specific training and special licensure, and who may be unavailable in acute detoxification units where patients receive treatment for acute opioid withdrawal.…”