A (very) Brief History of Electrical Vagus Nerve Stimulation

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Vagus nerve stimulation has a long precedence in medicine. As early as 1880, physicians noted that compression of the vagus nerve in the neck could abort seizures. It was not fully understood at first that this was specifically actuated by compression of the nerve rather than the carotid artery, which runs alongside the nerve, but instruments were developed nevertheless to help physicians administer such treatments. 

Electrical vagus nerve stimulation was first studied in the 1930s and 1940s. These, and subsequent, studies established a clear link between stimulation and effects on brain activity. Early studies on cats and monkeys demonstrated changes in neurological activity of the thalamus (one of the major gateway points for sensory information as it passes from the body into the brain) following vagal nerve stimulation [11]; and later studies demonstrated that seizures in dogs could be inhibited by direct stimulation of the cervical (along the neck) branch of the vagus nerve. 

Clinical Approval

Such studies laid the groundwork for further studies in humans which produced similar results; and following successful clinical trials, the FDA eventually approved the use of an implanted electrical vagus nerve stimulator for the treatment of certain types of epilepsy in 1997. The procedure involved implanting electrodes to fit around the vagus nerve in the neck along with a control device and battery implanted into the chest. The same mode of treatment was later also approved by the FDA for use in chronic, drug resistant depression.

 

Further uses of implanted electrical vagus stimulators have been investigated since, and have demonstrated success in a range of cases, though not all have so far received FDA approval – these include uses in the treatment of migraines, anxiety disorder, heart failure, bipolar disorder and obesity. 

Despite medical approval of such treatments, they are only used in serious cases because any implant carries considerable risks. The surgery itself presents a risk of infection; while the implant has associated side-effects, such as hoarseness resulting from damage to the vocal cords; and in a small number of cases, the surgery and the following treatment can result in complete paralysis of the vocal cords. 

Such negative complications from invasive treatments have led to greater investigation of non-invasive alternatives. 

Transcutaneous Vagus Nerve Stimulation

Transcutaneous (through the skin) vagus nerve stimulation (tVNS) is emerging as just such an alternative. It seeks to administer electrical stimulation to the vagus nerve without the need for implant surgery, thus avoiding the associated risks. 

One of the earliest forms of tVNS was administered at a similar location to the original implants, namely the cervical branch of the vagus. The electrodes of the stimulator are pressed against the skin and the current is passed through the skin to stimulate the nerve. 

The treatment has proved an effective alternative to implants, but still presents some challenges. For example, the cervical branch of the vagus nerve is relatively deep in the body and is contained within the carotid arterial sheath. It therefore requires high intensity stimulation which, at some frequencies, can be painful to subjects. Companies working on this form of treatment have found methods of stimulation to circumvent these issues; but other researchers still wondered if other methods may be possible, or even preferable [9]. 

Spurred by these considerations, scientists and clinicians have increasingly investigated the use of the auricular branch of the vagus nerve, which runs far closer to the skin and is more easily accessed through the ear. Some evidence suggests that it may indeed be a better location for stimulation than the cervical branch, either transcutaneously or subcutaneously [9]. 

Auricular tVNS

The outer ear is actually supplied by a number of nerves, one of which is the vagus nerve. As the vagus nerve leaves the brain, it branches down into the neck (the cervical branch) and up into the ear (the auricular branch). At the tragus and concha of the ear, the nerve is particularly close to the surface of the skin and presents an ideally accessible location at which vagus nerve stimulation can be administered [7]. 

As early as 2001, researchers showed that electrical stimulation of the vagus nerve at the tragus using a form of electroacupuncture reduced the dependence of patients with coronary arterial disease on vasodilator medication [12].

Further studies followed from these and showed that stimulation of the vagus nerve via the ear triggered neurological and physiological responses very similar to cervical electrical stimulation [8] and the European Union eventually certified it as an alternative treatment for epilepsy and pain in 2010 and 2012 respectively.

Given such clear evidence of the medical benefits of electrical vagus nerve stimulation in severe cases, researchers naturally began to ask questions about the possible health and well being benefits to people with milder conditions or as a preventative treatment. Much of this research continued in parallel with medical research into the more serious medical cases. 

Health Benefits

Our earlier post explained some of the links between low vagus nerve activity, often referred to as vagal tone, and poor health outcomes. Some of the latest evidence shows that daily tVNS via the ear can provide significant benefit, with the greatest benefit accruing to those with the lowest vagal tone [13].

Over several years, researchers from two leading UK universities showed first (in 2017) that just 15 minutes of daily tVNS applied to the tragus of the ear improved vagus nerve function in young people, then in a followup study (2019) they showed that the effects were greatest when applied to a cohort of over 55s [14]. 

As we age our vagal tone naturally declines and causes a decline in various health measures. The health outcomes are not immediately severe but do cause a decline in quality of life as measured by sleep, mood, endurance, immune system strength and cognitive functions such as memory. All these measures were improved in the test cohort. 

Promising research such as this led to the foundation of vagus.net. 

tVNS is still very much an emerging technology and it is very likely that as more research is done we will increasingly learn more about the underlying physiological and neurological mechanisms controlling the observed effects. But even at this early stage, it is clear that people of any age can benefit greatly from this treatment. It is our goal at vagus.net to make this technology as accessible as possible to as many people as possible. We’ll be following the science so that you don’t have to and you can always check back here to discover the latest developments. 

As new research emerges, we will be constantly working to try and make this as available as possible to the general public so you can benefit directly from the best and most current science. 

References

[1] Howland, Robert H. “Vagus Nerve Stimulation.” Current behavioral neuroscience reports vol. 1,2 (2014): 64-73. doi:10.1007/s40473-014-0010-5

[2] Frieda A. Koopman, Sangeeta S. Chavan, Sanda Miljko, Simeon Grazio, Sekib Sokolovic, P. Richard Schuurman, Ashesh D. Mehta, Yaakov A. Levine, Michael Faltys, Ralph Zitnik, Kevin J. Tracey, Paul P. Tak (2016), Vagus nerve suppression of cytokines in humans. Proceedings of the National Academy of Sciences Jul 2016, 201605635; DOI: 10.1073/pnas.1605635113

[3] Lanska DJ. J.L. Corning and vagal nerve stimulation for seizures in the 1880s. Neurology. 2002;58(3):452-459. doi:10.1212/wnl.58.3.452

[4] Zabara J. Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia. 1992;33(6):1005-1012. doi:10.1111/j.1528-1157.1992.tb01751.x

[5] Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81(16):1453-1459. doi:10.1212/WNL.0b013e3182a393d1

[6] Rogers A.J., Baykaner T., Narayan S.M. The interconnected atrium: Acute impact of pulmonary vein isolation on remote atrial tissue. Journal of Cardiovascular Electrophysiology, Volume 31, 2020

[7] Ellrich J. Transcutaneous vagus nerve stimulation. Eur Neurological Rev. 2011;6(4):254–256.

[8] Dietrich S, Smith J, Scherzinger C, et al. A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI. Biomed Tech (Berl). 2008;53(3):104-111. doi:10.1515/BMT.2008.022

[9] Murray AR, Atkinson L, Mahadi MK, Deuchars SA, Deuchars J. The strange case of the ear and the heart: the auricular vagus nerve and its influence on cardiac control. Auton Neurosci. 2016; 199:48–53.

[10] Lanska DJ. J.L. Corning and vagal nerve stimulation for seizures in the 1880s. Neurology. 2002;58(3):452-459. doi:10.1212/wnl.58.3.452

[11] Juhász G, Détári L, Kukorelli T. Effects of hypnogenic vagal stimulation on thalamic neuronal activity in cats. Brain Res Bull. 1985;15(5):437-441. doi:10.1016/0361-9230(85)90032-2

[12] Zamotrinsky AV, Kondratiev B & de Jong JW (2001). Vagal neurostimulation in patients with coronary artery disease. Auton Neurosci 88, 109.

[13] Deuchars, S.A., Lall, V.K., Clancy, J., Mahadi, M., Murray, A., Peers, L. and Deuchars, J. (2018), Mechanisms underpinning sympathetic nervous activity and its modulation using transcutaneous vagus nerve stimulation. Exp Physiol, 103: 326-331. doi:10.1113/EP086433

[14] Bretherton B, Atkinson L, Murray A, Clancy J, Deuchars S, Deuchars J. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation. Aging (Albany NY). 2019; 11:4836-4857. https://doi.org/10.18632/aging.102074

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Getting On Your Nerves

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