Category Archives: Vagus Nerve Stimulation

Vagus Nerve Stimulation And Inflammation

Non-Invasive Vagus Nerve Stimulation Conceptual Representation
Non-Invasive Vagus Nerve Stimulation Conceptual Representation

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a medical treatment that is routinely used in the treatment of epilepsy and other neurological conditions. VNS studies are not just clinically, but also scientifically informative regarding the role of the vagus nerve in health and disease.

Vagus Nerve Stimulation Device and Method

Non-Invasive Vagus Nerve Stimulator Attached to the Auricular Concha via Ear Clip
Non-Invasive Vagus Nerve Stimulator Attached to the Auricular Concha via Ear Clip

Vagus nerve stimulation works by applying electrical impulses to the vagus nerve. The stimulation of the vagus nerve can be performed in two different ways: a direct invasive stimulation, which is currently the most frequent application and an indirect transcutaneous non-invasive stimulation. Invasive VNS (iVNS) requires the surgical implantation of a small pulse generator subcutaneously in the left thoracic region. In contrast to iVNS, transcutaneous VNS (tVNS) allows for a non-invasive stimulation of the vagus nerve without any surgical procedure. Here, the stimulator is usually attached to the auricular concha via ear clips and delivers electrical impulses at the subcutaneous course of the afferent auricular branch of the vagus nerve (2).

A pilot study that examined the application of VNS in 60 patients with treatment-resistant depressive disorder showed a significant clinical improvement in 30–37% of patients and a high tolerability (3). Five years later, the stimulation of the vagus nerve for the treatment of refractory depression was approved by the U.S. Food and Drug Administration (FDA) (4). Since then, the safety and efficacy of VNS in depression has been demonstrated in numerous observational studies as can be seen below. In contrast, there is no randomized, placebo-control clinical trial that reliably demonstrates antidepressant effects of VNS.

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

VNS In Inflammatory Bowel Disease (IBD)

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin (5) and intestinal inflammation (6). The VNs also indirectly modulates immune activity of the spleen through connections with the splenic sympathetic nerve (7). In rats with colonic inflammation, the 3-hour long daily VNS for a period of 5 days led to a reduction in inflammatory markers and an improvement in symptoms of colitis (8).

Vagus nerve stimulation should be of interest in other inflammatory diseases, such as rheumatoid arthritis, another TNF-α-mediated disease. In patients with rheumatoid arthritis, a study that demonstrated an improvement of symptoms in the early and late stages of the disease through 1–4 minutes of VNS daily (9). This study was also the first to show that VNS inhibits the production of TNF-α (also known as TNF-alpha) and other cytokines in humans by stimulating the inflammatory reflex, leading to an improvement of symptom severity. These data argue for an anti-inflammatory role of the vagus nerve and provide potential therapeutic applications for patients with IBDs (10, 8, 11).

Conclusion

The interaction between the gut and the brain is based on a complex system that includes not only neural but also endocrine, immune, and humoral links.

The vagus nerve is an essential part of the brain–gut axis and plays an important role in the modulation of inflammation, the maintenance of intestinal homeostasis, and the regulation of food intake, satiety, and energy homeostasis. An interaction between nutrition and the vagus nerve is well known, and vagal tone can influence food intake and weight gain.

Moreover, the vagus nerve plays an important role in the pathogenesis of psychiatric disorders, obesity as well as other stress-induced and inflammatory diseases.

Vagus nerve stimulation and several meditation techniques demonstrate that modulating the vagus nerve has a therapeutic effect, mainly due to its relaxing and anti-inflammatory properties.

Extinction paired with VNS is more rapid than extinction paired with sham stimulation. As it is currently approved by the Federal FDA for depression and seizure prevention, VNS is a readily available and promising adjunct to exposure therapy for the treatment of severe anxiety disorders.

Vagus nerve stimulation is an effective anticonvulsant device and has shown in observational studies antidepressant effects in chronic treatment-resistant depression. Because the vagus nerve sends information to brain regions is important in the stress response (LC, orbitofrontal cortex, insula, hippocampus, and amygdala), this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize stress-related disorders.

Psychotropic drugs, such as serotonin reuptake inhibitors, have effects on both the brain and the gastrointestinal tract and consequently should be understood as modulators of the brain–gut axis.

Research investigating the interaction between nutritive factors, somatic factors, such as heart rate, psychological and pharmacological treatments, and vagal activity has the potential to lead to integrative treatment options that incorporate VNS, nutritional approaches, drugs, and psychological interventions, such as mindfulness-based approaches, which can be tailored to the needs of the individual patient.

A Final Thought About Vagus Nerve Stimulation And CES

Cranial Electrotherapy Stimulation (CES) has been engaging Vagus nerve stimulation for decades, through the use of ear clips to stimulate the nerve endings in the ears. Recent data from clinical studies and practical application reflect the positive results that may be gained by applying low amplitude, extremely low frequency (ELF) electric currents, through the Vagus nerve system. The CES Ultra cranial electrotherapy stimulator device incorporates both ELF and ear clip attachments, as part of its standard application to treat anxiety and insomnia without medication.

Get Your Own CES Ultra for only $299
Rated 4.8/5 based on 18 user reviews

Several months ago I suffered with severe insomnia. I couldn’t get more than 3 or 4 hours of sleep a night, and sometimes I couldn’t sleep at all. I tried all kinds of sleep medications and supplements without success. I saw a neurologist who specializes in sleep problems, but she was of little help. I did some research on the internet and came across studies with CES. I decided to buy a CES Ultra. Within 2 weeks I was able to get 7 hours of sleep a night. I used it every day for two months and during that time I had no insomnia. Now I find that using it 2 or 3 times a week is sufficient for me to get a good night’s sleep.

Ray W.

Citations

  1. Frontiers in Psychiatry – Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (original publication)
  2. National Center for Biotechnology Information, U.S. National Library of Medicine – Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study
  3. Springer Nature – Vagus Nerve Stimulation (VNS™) for Treatment-Resistant Depression: Efficacy, Side Effects, and Predictors of Outcome
  4. ScienceDirect® – Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review
  5. Springer Nature – Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
  6. Springer Nature – Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway
  7. American Association for the Advancement of Science – Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit
  8. ScienceDirect – Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease
  9. PNAS – Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis
  10. The Physiological Society – Anti‐inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation
  11. Clinical Medicine Insights: Gastroenterology – Bioelectrical Stimulation for the Reduction of Inflammation in Inflammatory Bowel Disease
  12. Medium Elemental – Science Confirms That the Vagus Nerve Is Key to Well-being
  13. CES Ultra – The Role of CES in Fighting Inflammation
  14. CES Ultra – Non-Drug Relief From Anxiety.

Last Modified: March 23, 2021

Great Neuroscience Discoveries of 2018

2018 was when neuroscience made the impossible possible. Here are four neuroscience findings from 2018 that still blow our minds as we kick off the New Year.

Electrical implant restores walking in paralyzed patients

2018 was, without doubt, a breakthrough year for restoring mobility in paralyzed patients.

The technology is several years in the making, with initial positive results in monkeys. It works by implanting a neuroprosthesis into the spinal cord to bypass the site of injury by artificially stimulating remaining nerves.

In September, the Mayo Clinic reported the extraordinary case of Jered Chinnock, who was paralyzed at the waist in 2013. After getting the implant, he walked half the length of a football field. Another report showed that electrical stimulation in four cases was able to help some paralyzed patients go home and get around with only a walker.

Less than a month later, yet another team reported that electrical stimulation using a wireless implant helped three paralyzed patients walk with the aid of crutches or a walker. After a few months of training, the patients could more easily move around even when the stimulation was off, suggesting that the regime had helped remaining healthy nerves rework their connections to adapt and heal.

Electrical stimulation isn’t the only treatment in the works. Another study found that human stem cells, when implanted into monkeys, could synapse with the recipient’s own neurons and restore natural movement after spinal cord injury. These therapies—although expensive and in their infancy—lay a promising road ahead for returning mobility to paralyzed patients.

CRISPR barcodes map brain development in exquisite detail

The developing mammalian brain consists of an intricately-choreographed dance of newborn neurons, with each adopting its specific identity and migrating to its home base in the brain. Scientists have long hoped to examine the process in detail, which could help uncover secrets of brain development—and how it goes wrong.

Perhaps unsurprisingly, tracing the history of every single one of the billions of developing cells in the brain has been impossible—until CRISPR came along.

Last August, a team used CRISPR to generate a unique genetic barcode for every single cell in the mouse brain. By reading the barcodes, scientists were able to retrace a cell’s entire history in the developing brain. Like genetic sleuths, the scientists reconstructed entire cellular family trees to show how cells relate to one another.

A new type of neuron in the cortex that’s potentially uniquely human

Perhaps shockingly, even today neuroscientists are still uncovering new cellular components that make up our mighty brains. Last year saw the discovery of giant neurons within the claustrum, a thin sheet of cells that some believe is the seat of consciousness.

This year, the Allen Institute in Seattle is back at it with another finding: rosehip neurons, each containing dense bundles of processes around the cell’s center that make it look like a rose after shedding its petals.

These neurons make up nearly 15 percent of neurons in the outermost layer of the brain that supports high-level cognitive functions. Remarkably, rosehip neurons have never before been seen in mice or other well-studied lab animals. Although the team can’t yet fully conclude that they’re specific to humans, their scarcity within the animal kingdom is intriguing.

The next step is figuring out the functions of these rose-like neurons—in particular, are they partly why our brains are special?—and whether they are linked to neuropsychiatric disorders.

Gut-brain connection grows stronger with direct anatomical link

One of the hottest research trends in neuroscience is the link between the brain and the gut—often dubbed the “little brain.”

The human gut is lined with over 100 million nerve cells that allow it to talk to the brain, letting us know when we’re hungry or when we’ve over-indulged. But it’s not all digestion: scientists are increasingly realizing that the gut could contribute to anxiety, depression, or more controversially, cognition.

Last year scientists found a new set of informational highways that directly link the gut to the brain. Within the gut, enteroendocrine cells pump out hormones that kick off digestion and suppress hunger. These cells have little foot-like protrusions that look remarkably like synapses—the structure that neurons use to talk to each other using chemicals.

With the help of a glow-in-the-dark rabies virus, which can jump from synapse to synapse, the team found that enteroendocrine cells directly link to neurons in the vagus nerve—a giant nerve that runs from the brain to vital organs such as the heart and lungs. What’s more, they chat with their partners using classical neurotransmitters including glutamate and serotonin, which work much faster than hormones.

Another study found that the gut directly links to the brain’s reward centers through the vagus nerve. Using lasers to zap sensory neurons in the gut of mice, the scientists found increased levels of mood-boosting dopamine in their brains.

These new connections could explain why vagus nerve stimulation is potentially helpful for those with severe depression. More relevant to the holiday season, it also could explain why eating makes us feel warm and fuzzy.

Uncovering the gut-brain connection is gaining steam as a research field. Eventually, the findings could lead to new treatments for disorders linked to a malfunctioning gut—for example, obesity, eating disorders, depression, or even autism.

ref:. singularityhub.com | discoverieshub.com

Vagus Nerve Stimulation Reduces Inflammation and the Symptoms of Arthritis

Vagus Nerve Stimulator Usage: Gelled Electrode, Surgically Implanted, Ear-Clip Placement
Vagus Nerve Stimulator Usage: Gelled Electrode (left), Surgically Implanted Stimulator (center), Ear-Clip Placement (right)

Note: The CES Ultra does not make claims as to alleviation of pain. However this article shows how inflammation and symptoms of arthritis may be reduced by Vagus nerve stimulation. The CES Ultra targets the Vagus nerve.

Inflammatory responses play a central role in the development and persistence of many diseases and can lead to debilitating chronic pain. In many cases, inflammation is your body’s response to stress. Therefore, reducing fight-or-flight responses in the nervous system and lowering biological markers for stress can also reduce inflammation.

Typically, doctors prescribe medications to combat inflammation. However, there is continual growing evidence showing that another way to combat inflammation is by engaging the Vagus nerve and improving vagal tone. This can be achieved through daily habits such as yoga and meditation — or in more extreme cases of inflammation, such as rheumatoid arthritis (RA) — by using an implanted device for Vagus nerve stimulation (VNS).

The Vagus nerve is known as the wandering nerve because it has multiple branches that diverge from two thick stems rooted in the cerebellum and brainstem that wander to the lowest viscera of your abdomen touching your heart and most major organs along the way. Vagus means wandering in Latin. The words vagabond, vague, and vagrant are all derived from the same Latin root.

In 1921, a German physiologist named Otto Loewi discovered that stimulating the Vagus nerve caused a reduction in heart rate by triggering the release of a substance he coined Vagusstoff (German for Vagus Substance). The Vagus substance was later identified as acetylcholine and became the first neurotransmitter ever identified by scientists.

Vagusstoff (acetylcholine) is like a tranquilizer that you can self-administer simply by taking a few deep breaths with long exhales. Consciously tapping into the power of your Vagus nerve can create a state of inner-calm while taming your inflammation reflex.

The Vagus nerve is the prime component of the parasympathetic nervous system which regulates the rest-and-digest or tend-and-befriend responses. On the flip side, to maintain homeostasis, the sympathetic nervous system drives the fight-or-flight response.

Healthy Vagal Tone Is Part of a Feedback Loop Linked to Positive Emotions

Healthy vagal tone is indicated by a slight increase of heart rate when you inhale, and a decrease of heart rate when you exhale. Deep diaphragmatic breathing—with a long, slow exhale—is key to stimulating the Vagus nerve and slowing heart rate and blood pressure, especially in times of performance anxiety.

A higher vagal tone index is linked to physical and psychological well-being. Conversely, a low vagal tone index is associated with inflammation, depression, negative moods, loneliness, heart attacks, and stroke.

Discover the benefits of Vagus nerve stimulation. They describe a costly and intrusive procedure involving an implant. Cranial Electrotherapy Stimulation (CES), specifically the CES Ultra device, can achieve the same result at fraction of the cost and in a noninvasive manner.

Rheumatoid Arthritis (RA) and Vagus Nerve Stimulation

Recently, an international team of researchers from Amsterdam and the United States conducted a clinical trial which demonstrates that stimulating the Vagus nerve with a small implanted device significantly reduced inflammation and improved outcomes for patients with rheumatoid arthritis by inhibiting cytokine production.

RA is a chronic inflammatory disease that affects approximately 1.3 million people in the United States and costs tens of billions of dollars to treat each year, according to researchers.

Firing Vagus Nerve Cells Illustration
Firing Vagus Nerve Cells Illustration

The neuroscientists and immunology experts involved in this study used state-of-the-art technology to map the neural circuitry that regulates inflammation. In one circuit—termed the inflammatory reflex—action potentials transmitted in the Vagus nerve inhibit the production of pro-inflammatory cytokines.

This was the first human study designed to reduce symptoms of rheumatoid arthritis by stimulating the Vagus nerve with a small implanted device which triggered a chain reaction that reduced cytokine levels and inflammation. Although this study focused on rheumatoid arthritis, the trial’s results may have implications for patients suffering from other inflammatory diseases, including Parkinson’s, Crohn’s, and Alzheimer’s.

These findings suggest a new approach to fighting diseases that are currently treated with relatively expensive drugs that have a host of side effects. VNS gives healthcare providers a potentially more effective way to improve the lives of people suffering from chronic inflammatory diseases.

Conclusion: Vagus Nerve Stimulation Is a Potent Drug-Free Alternative for Treating Inflammation

Co-author Kevin J. Tracey, president and CEO of the Feinstein Institute for Medical Research and the person who discovered the inflammatory reflex, said, – This is a real breakthrough in our ability to help people suffering from inflammatory diseases. While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the Vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself.

CES has been engaging Vagus nerve stimulation for decades, through the use of ear clips to stimulate the nerve endings in the ears. Positive results may be gained by applying low amplitude, extremely low frequency (ELF) electric currents, through the Vagus nerve system. The CES Ultra cranial electrotherapy stimulator device incorporates the use of ELF applied by ear clip attachments or gelled electrodes, to stimulate the Vagus nerve.

Get Your Own CES Ultra for only $299
Rated 4.8/5 based on 18 user reviews

…CES has also been shown to reduce muscular tension. I often recommend it to patients who have been injured in automobile accidents, as its gentle and relaxing effects help them to overcome not only the emotional impact of the accident, but reduce their perception of pain as well.

Psychologist, Canada

Citations

Last Modified: March 20, 2021

The CES Ultra and the Ear – Part 1

PART 1 PART 2

The CES ultra underscores its use of its conductive rubber ear clips. The rationale behind it is some interesting science on the ear; especially the vagus nerve and the special role it plays in the body. Read on.

Ref: Wandering nerve could lead to range of therapies

With outposts in nearly every organ and a direct line into the brain stem, the vagus nerve is the nervous system’s superhighway. About 80 percent of its nerve fibers — or four of its five “lanes” — drive information from the body to the brain. Its fifth lane runs in the opposite direction, shuttling signals from the brain throughout the body.

Doctors have long exploited the nerve’s influence on the brain to combat epilepsy and depression. Electrical stimulation of the vagus through a surgically implanted device has already been approved by the U.S. Food and Drug Administration as a therapy for patients who don’t get relief from existing treatments.

Now, researchers are taking a closer look at the nerve to see if stimulating its fibers can improve treatments for rheumatoid arthritis,
SUPER-HIGHWAY The vagus nerve runs from the brain stem down the neck and into the abdomen, reaching a slew of organs in the process.
Nicole Rager Fuller
heart failure, diabetes and even intractable hiccups. In one recent study, vagus stimulation made damaged hearts beat more regularly and pump blood more efficiently. Researchers are now testing new tools to replace implants with external zappers that stimulate the nerve through the skin.

But there’s a lot left to learn. While studies continue to explore its broad potential, much about the vagus remains a mystery. In some cases, it’s not yet clear exactly how the nerve exerts its influence. And researchers are still figuring out where and how to best apply electricity.

“The vagus has far-reaching effects,” says electrophysiologist Douglas Zipes of Indiana University in Indianapolis. “We’re only beginning to understand them.”

The wanderer

Anchored in the brain stem, the vagus travels through the neck and into the chest, splitting into the left vagus and the right vagus. Each of these roads is composed of tens of thousands of nerve fibers that branch into the heart, lungs, stomach, pancreas and nearly every other organ in the abdomen. This broad meandering earned the nerve its name — vagus means “wandering” in Latin — and enables its diverse influence.

cesultra-ear-nerve

The nerve plays a role in a vast range of the body’s functions. It controls heart rate and blood pressure as well as digestion, inflammation and immunity. It’s even responsible for sweating and the gag reflex. “The vagus is a huge communicator between the brain and the rest of the body,” says cardiologist Brian Olshansky of the University of Iowa in Iowa City. “There really isn’t any other nerve like that.”

The FDA approved the first surgically implanted vagus nerve stimulator for epilepsy in 1997. Data from 15 years of vagus nerve stimulation in 59 patients at one hospital suggest that the implant is a safe, effective approach for combating epilepsy in some people, researchers in Spain reported in Clinical Neurology and Neurosurgery in October. Twenty of the patients experienced at least 50 percent fewer seizures; two of those had a 90 percent drop in seizures. The most common side effects were hoarseness, neck pain and coughing. In other research, those effects often subsided when stimulation was stopped.

Early on, researchers studying the effects of vagus stimulation on epilepsy noticed that patients experienced a benefit unrelated to seizure reduction: Their moods improved. Subsequent studies in adults without epilepsy found similar effects. In 2005, the FDA approved vagus nerve stimulation to treat drug-resistant depression.

Although many details about how stimulation affects the brain remain unclear, studies suggest that vagus stimulation increases levels of the neurotransmitter norepinephrine, which carries messages between nerve cells in parts of the brain implicated in mood disorders. Some antidepressant drugs work by boosting levels of norepinephrine. Silencing norepinephrine-producing brain cells in rats erased the antidepressant effect of vagus nerve stimulation, scientists reported in the Journal of Psychiatric Research in September.

Against the swell

Vagus stimulation for epilepsy and depression attempts to target the nerve fibers that shuttle information from body to brain. But its fifth lane, which carries signals from brain to body, is a major conductor of messages controlling the body’s involuntary functions, including heart rhythms and gut activity. The nerve’s southbound fibers can also be a valuable target for stimulation.

Around 15 years ago, scientists determined that the brain-to-body lane of the vagus plays a crucial role in controlling inflammation. While testing the effects of an anti-inflammatory drug in rats, neurosurgeon Kevin Tracey and his colleagues found that a tiny amount of the drug in the rats’ brains blocked the production of an inflammatory molecule in the liver and spleen. The researchers began cutting nerves one at a time to find the ones responsible for transmitting the anti-inflammatory signal from brain to body.

“When we cut the vagus nerve, which runs from the brain stem down to the spleen, the effect was gone,” says Tracey, president and CEO of the Feinstein Institute for Medical Research in Manhasset, N.Y. Later research indicated that stimulating undamaged vagus fibers also had anti-inflammatory effects in animals.

Vagus stimulation prompts release of acetylcholine, Tracey and colleagues reported in 2000. Acetylcholine, a neurotransmitter like norepinephrine, can prevent inflammation.

In 2011, rheumatologist Paul-Peter Tak, of the University of Amsterdam, and his colleagues implanted vagus nerve stimulators into four men and four women who had rheumatoid arthritis, an autoimmune inflammatory condition that causes swollen, tender joints. After 42 days of vagus stimulation — one to four minutes per day — six of the eight arthritis patients experienced at least a 20 percent improvement in their pain and swelling. Two of the six had complete remission, the researchers reported at an American College of Rheumatology conference in 2012.

“From a scientific perspective, it’s an extremely exciting result,” says Tak, who is also a senior vice president at GlaxoSmithKline pharmaceuticals based in Stevenage, England. Despite advances in treatments over the last two decades, rheumatoid arthritis patients need better options, he says. In 2014, Tak and his colleagues reported that vagus stimulation reduced inflammation and joint damage in rats with arthritis. After a week of once-daily, minute-long stimulation sessions, swelling in the rats’ ankles shrank by more than 50 percent, the scientists reported in PLOS ONE.

If these results hold up in future studies, Tak hopes to see the procedure tested in a range of other chronic inflammatory illnesses, including inflammatory bowel disorders such as Crohn’s disease. Studies in animals have shown promise in this area: In 2011, researchers reported in Autonomic Neuroscience: Basic and Clinical that vagus stimulation prevented weight loss in rats with inflamed colons.

Treating inflammatory conditions with vagus stimulation is fundamentally different from treating epilepsy or depression, Tak says. More research with patients will be necessary to develop the technique. “We are entering a completely unknown area, because it’s such a new approach,” he says. There could be financial hurdles as well, he says. But GlaxoSmithKline, which Tak joined after initiating the arthritis study, has purchased shares of SetPoint Medical, a company in Valencia, Calif., that produces implantable vagus nerve stimulators, Tak says.

As he and others put stimulation to the test for inflammation, some scientists are attempting to see if manipulating the nerve can help heal the heart.

Read more Part 2

The CES Ultra and the Ear – Part 2

PART 1 PART 2

The CES ultra underscores its use of its conductive rubber ear clips. The rationale behind it is some interesting science on the ear; especially the vagus nerve and the special role it plays in the body. Read on.

Ref: Wandering nerve could lead to range of therapies

Taking heart

The vagus nerve has profound control over heart rate and blood pressure. Patients with heart failure, in which the heart fails to pump enough blood through the body, tend to have less active vagus nerves. Trying to correct the problem with electrical stimulation makes sense, says Michael Lauer, director of the cardiovascular sciences division at the National Heart, Lung and Blood Institute in Bethesda, MD. “It’s a great idea.”

cesulyra-ear-clips

Yet so far, results from studies on the effects of vagus stimulation on heart failure have been inconsistent. In 2011, researchers reported in the European Heart Journal that repeated vagus nerve stimulation improved quality of life and the heart’s blood-pumping efficiency in heart failure patients. A vagus stimulation trial of heart failure patients in India published in the Journal of Cardiac Failure in 2014 echoed these results. After six months of therapy, the patients’ left ventricles pumped an average of 4.5 percent more blood per beat.

Last August, however, researchers reported that a six-month clinical trial of vagus stimulation failed to improve heart function in heart failure patients in Europe. This study had the most participants — 87 — but used the lowest average level of electrical stimulation. “All the results thus far are preliminary. The studies that have been finished to date are relatively small,” Lauer says. “But there certainly are promising findings that [suggest] we may be barking up the right tree.”

Another group of scientists is testing more intense vagus stimulation for patients with heart failure. The trial, called INOVATE-HF, is funded by the Israeli medical device company BioControl Medical and uses a higher level of electrical current than the European study that showed no measurable improvements.

“If you try to lower blood pressure and you take a quarter of a pill instead of one pill, blood pressure won’t change,” says cardiologist Peter Schwartz of the IRCCS Istituto Auxologico Italiano in Milan. It’s equally important to use the right dose of vagus stimulation, he says. The new trial is also much larger than earlier studies, with more than 700 patients enrolled internationally. Results are expected by the end of 2016.

Vagus manipulation isn’t limited to heart failure research. It’s also being tried in atrial fibrillation, in which the heart flutters erratically. “When it flutters, it doesn’t really push blood very efficiently,” says clinical electrophysiologist Benjamin Scherlag of the University of Oklahoma in Oklahoma City. Atrial fibrillation is common in people over age 60, Scherlag says, and can ultimately lead to blood clots and strokes. Treatments include drugs that alter heart rhythm or thin the blood, but they don’t work for all patients and some have nasty side effects, Scherlag says.

In the lab, scientists can use high-intensity vagus stimulation to alter heart rhythm and induce atrial fibrillation in animals. But milder stimulation that alters heart rate only slightly, if at all, can actually quell atrial fibrillation, animal studies and one human study show.

Vagus stimulation for atrial fibrillation is still in its infancy, and clinical applications haven’t been adequately tested, says Indiana’s Zipes. “Nevertheless, the concept bears looking into.”

Skin deep

“Vagal nerve stimulation is very nice, but in order to get to the vagus nerve … you have to cut down surgically,” Scherlag says. “This is not the kind of thing you want to do, except under extreme situations.”

cesulyra-ear-clips

But in the ear, tiny fingers of the vagus’s fibers run close to the surface of the skin, primarily under the small flap of flesh, the tragus, that covers the ear’s opening. Studies have explored using stimulation of those fibers through the skin of the ear to treat heart failure, epilepsy and depression, as well as memory loss, headaches and even diabetes — a reflection of the nerve’s control over a variety of hormones in addition to acetylcholine and norepinephrine.

Stimulating the vagus nerve through the ear of diabetic rats lowered and controlled blood sugar concentrations, researchers from China and Boston reported in PLOS ONE in April. The stimulation prompted the rats’ bodies to release the hormone melatonin, which controls other hormones that regulate blood sugar.

Ear-based vagus stimulation appeared to improve memory slightly in 30 older adults in the Netherlands. After stimulation, study subjects were better able to recall whether they had been shown a particular face before, says study coauthor Heidi Jacobs, a clinical neuroscientist at Maastricht University in the Netherlands. The researchers, who reported the work in the May Neurobiology of Aging, plan to investigate whether these effects last over time and exactly how the stimulation affects the brain, Jacobs says.

The ear isn’t the only nonsurgical target. The company electroCore, based in Basking Ridge, N.J., manufactures a small, handheld device that can stimulate the vagus when placed on the throat. The company initially tested the devices to reduce asthma symptoms — relying on the nerve’s anti-inflammatory action. But during testing, patients reported that their headaches were disappearing, says J.P. Errico, CEO of electroCore. Now, the company is investigating the use of an electroCore device to treat chronic cluster headaches, severe headache attacks that can come and go for over a year. People suffering from an average of 67.3 cluster headaches each month experienced around four fewer attacks per week on average when using the device along with standard treatments like drugs, researchers reported in Cephalalgia in September.

Beyond the mystery switch

Even for depression and epilepsy, Tak says, researchers still need to figure out the best ways of stimulating the vagus — exactly where to place a device, and how much of a shock to deliver.

The nerve’s multitasking, two-way nature makes it a challenge to fully understand and control. It’s hard to know exactly what you’re zapping when you stimulate the vagus nerve, says physiologist Gareth Ackland of University College London. He compares vagus stimulation to flipping on a light switch in one room of a house and discovering that this endows other rooms in the house with magical powers. “I’m not sure which room it’s going to happen in, I’m not sure for how long and I’m not sure if, after a while, it’s going to work or not,” he says.

The intensity of electrical current, duration of stimulation and each patient’s health status could all affect the results of a vagus stimulation trial, Ackland says. And it’s possible that a widespread effect, such as suppressing inflammation caused by the immune system, could even be harmful to some patients.

Ackland says that he and his colleagues agree that the vagus nerve is important. And he’s not ready to discount vagus stimulation as a potential therapy for conditions such as heart failure. But he warns that there’s a good deal of biology left to understand. “There’s an awful lot of basic science and basic clinical research that is needed before launching into a variety of potential interventions,” he says.

For Tracey, it’s about way more than the vagus. “Nobody should overpromise that the vagus nerve is the secret to everything,” he says. But with a better map of the body’s nerves and their functions, the lessons learned by studying the vagus could inform future therapies that use nerve stimulation, he says. If researchers can understand and manipulate a particular circuit in a nerve that controls a specific molecule — for example, a protein involved in pain or even cell division — they could zero in on crucial targets. “The promise,” he says, “is for tremendous precision.”

Go back to PART 1