Category Archives: Inflammation

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, depression, and insomnia without medication.

Get Your Own CES Ultra for only $299

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. CES Ultra – The Role of CES in Fighting Inflammation
  13. CES Ultra – Non-Drug Relief From Anxiety.

Last Modified: December 4, 2019

Clinical trial of Cranial Electrotherapy stimulation in adolescent patient with depression, anxiety and developmental deviation

Vignette # 3:

Justin is a sixteen year old Caucasian male with a history of psychiatric treatment including medication intervention for developmental deviation with a hyperkinetic element. His history of school functioning had been very poor with low motivation to succeed. His father reports that Justin would often experience feelings of anger and anxiety with behavioral acting out. During the initial psychological evaluation he had great difficulty attending to tasks presented to him, was emotionally labile, and on a measure of depression he scored at the 24th percentile, while on a measure of anxiety he scored at the 2nd percentile with present moment (state) anxiety and at the 27th percentile with general proneness (trait) anxiety. On the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Full Scale intellectual functioning was in the Average range (Full Scale IQ = 96) with verbal area functioning in the Low Average range (Verbal IQ = 81) and performance area functioning in the Superior range (Performance IQ = 122).

After thirty days daily usage of at least forty-five minutes with the CES device he was again administered a psychological evaluation. On the same measure of depression Justin scored at the 1st percentile, while on the same measure of anxiety he scored at the 3rd percentile with present moment (state) anxiety and at the 16th percentile with general proneness (trait) anxiety, a noticeable decrease with his levels of depression and trait anxiety. On the WAIS-R Full Scale intellectual functioning was in the High Average range (Full Scale IQ = 111) with verbal area functioning in the Low Average range (Verbal IQ = 88) and Performance area functioning in the Very Superior range (Performance IQ = 139). Higher scores in the Verbal, Performance, and Full Scale areas indicated a gain of more than three standard deviations which by chance alone would occur in less than two in ten thousand cases (p<.0002). He was observed to be much more at ease with a noticeable improvement in his affect and cooperativeness as well as his ability to not only stay on task, but more motivation to do well with tasks. His mother stated that his ability to tolerate difficult situations and tasks was greatly improved as was his mood and that it was much easier and more pleasant to be around him.

Dynamics of the Cranial Electrotherapy Stimulation Devices Market

ces-ultra

With the increasingly stressful lifestyle there is also rise in other types of disorders such as anxiety and sleep disorders. With the lack of sufficient treatments that address these disorders, cranial electrotherapy stimulation comes as an innovative and required treatment.

Cranial Electrotherapy Stimulation (CES) device is a small device that stimulates the cranium and brain with a current less than 4 mA, which cannot be sensed by the patient. The cranial electrotherapy stimulation is approved by the FDA for the treatment of insomnia, depression and anxiety. Besides, it has potential application in the treatment of a number of disorders such as attention deficit hyperactivity disorder (ADHA), obsessive-compulsive disorder, post-traumatic stress disorder (PTSD), cognitive dysfunction, traumatic brain injury, pain, enhancing attention and concentration, and for reducing assaultive behavior.

A relatively large number of the population across the globe is diagnosed with such disorders. A significant portion of the U.S. population is affected by poor mental health, which leads to development of various kinds of mental health disorders. The treatment method is complementary and an alternative of medicine. There are large number of clinical trials currently active, which have proved the CES device as an effective treatment method.

The increasing number of cases of poor mental health with the development of disorders such as depression, anxiety and other sleep disorders is driving the growth of the market. Although animal studies have proved this device to be effective, the adoption of these devices is affected due to lack of strong evidence in humans proving the efficacy of the devices in all or most of the cases. However, there are a number of new clinical trials in the recruiting stage, which may help fill the gap in the market.

Use of Cranial Electrotherapy Stimulation in Hospitals and the Growing Demand of Wearable Type of Devices

There are various types of cranial electrotherapy stimulator devices and they can be broadly classified based on the type of electrode placement, such as invasive or transcranial and non-invasive or wearable. The wearable type is the dominant segment in the market. The wearable type device is user-friendly and does not requires surgical insertion of the electrode. Most of the FDA-approved devices are suitable for the treatment of insomnia, depression and anxiety, as the prevalence of these disorders is increasing, in which depression is the most common and growing disorder in the young population. Since most of these devices are available only in prescribed hospitals and mental health clinics, they have a large scope as end-use segments in the market.

The CES Ultra is one of the three major cranial electrotherapy stimulation devices, namely the CES Ultra by Neuro-fitnesss LLC, Alpha-Stim M and the Alpha-Stim AID by Electromedical Products International (EPI), and the Fisher-Wallace Simulator.

The CES Ultra is most affordable and effective easy to use CES device. You can buy directly from us, Neuro-fitnesss LLC, the manufacturer, without a middleman, and save time and money.

Why Pay More?

A few words of advice if you’re looking to purchase a CES unit: There are only a few FDA approved companies selling CES in the U.S. Here are the companies and their devices:

  • Neuro-Fitness LLC/ CES Ultra
  • Fisher Wallace, Inc./Fisher-Wallace Stimulator
  • Electromedical Products International, Inc./Alpha-Stim

Below is a price comparison table:

ces-devices-prices

Do not be fooled into paying more, because you think more is better. The FDA (Food and Drug Administration) considers all approved CES units to be “substantially equivalent” to each other.

Note: *The CES Ultra is the premier unit on the market. It alone features the original 100 Hz configuration that most of the CES research has been done on. Other units may claim to carry the 100 Hz but no other unit has an accurate rendition of the configuration on which most of the research is based.

WARNING

Do not buy product that are not approved by FDA (The Food and Drug Administration)

You may also find certain “underground” instruments on the market, particularly on the Internet. Contrary to their anecdotal claims, most have no scientific evidence behind them. Many are nothing more than low-cost pulse generators of dubious quality, and have not been fully evaluated for either efficacy or safety. They are not registered with the FDA. Many are billed as “for research purposes only,” and cannot legally be called “medical devices” or make any medical claims. Many are from overseas and are of dubious quality.

Pharmaceuticals NO, Electroceuticals YES

Electroceuticals are a new category of therapeutic agents which act by targeting the neural circuits of organs. The therapy involves mapping the neural circuitry and delivering neural impulses to these specific targets.

ces-electroceuticals

Currently drugs rule the roost. Whatever cannot be treated by drugs is treated by interventions or surgery. Technically, all organs and functions are regulated through brain and nervous system; a circuits of neurons communicating through neural impulses. Even endocrine system is under control of central nervous system by a complex array of feed-back mechanisms. Furthermore, most drugs effect by either acting on final-receptors (neural) or endocrine mechanisms. But all known drugs and of-course surgeries or non-surgical interventions have definite side-effects, because their action cannot be exactly localized to the defective part or organ. In this context, imagine a day when instead of drugs, electrical impulses become the mainstay of medical therapy.
Instead of administering drugs, or doing complex procedures, the physicians may just administer electroceuticals which will target individual nerve fibres or specific brain circuits and be able to treat any condition. In other words, the neural impulses that control the body will be entrained to regain the lost function and reestablish a healthy balance. Thus they could regulate a host of bodily activities; food intake, cardiac activity, pancreatic activity, liver, kidney or spleen functions. They could even control inflammation and set right many pathologies like diabetes mellitus, obesity, hypertension, heart failure, cerebro-vascular and pulmonary diseases.

It is estimated that electroceuticals will become a mainstay of medical treatment over the next two decades, benefiting up to 2 billion people – a quarter of the global population – who are suffering from chronic diseases.
Electroceuticals is a recently coined term for an old therapeutic modality that broadly encompasses all bioelectronic medicine. It incluses any type of electrical stimulation to affect and modify functions of the body; neural implants such as cochlear implants, retinal implants or spinal cord stimulators for pain relief but also cardiac pacemakers and implantable defibrillators. Recently, the field has expanded to include deep brain stimulation and the electrical stimulation of the vagus nerve including cranial electrotherapy stimulation (CES).

CES work because the nervous system and tissues function electrochemically and can be modulated readily by electrical intervention. Low-frequency current effectively targets cell receptors, activating them through frequency matching in a manner similar to that of chemical ligands.

The sensation of pain is transmitted through the body along billions of nerve cells that are designed specifically to transmit messages through electrochemical signals. Physics controls chemical reactions in the body, and most bodily functions can be normalized electrically. It is the application protocol that affects the peripheral pain site directly and accesses the central nervous system by directing the current through the spine. Combining MET and CES addresses all 4 pain pathways: transduction, transmission, modulation, and perception.

The resultant central and peripheral effects of CES include calmness, relaxation, reduced agitation and aggression, stabilized mood, improved sleep, and reduced pain. Results will vary with the exact technology used, the pathology of the disease being treated, the overall health and hydration of the patient.
Therapeutically, electroceuticals score over conventional drugs in a number of ways. Number one, they target neural electrical circuits which are composed of discrete elements; a system of – interconnected cells, nerve fibre network and nerve bundles, thus allowing for precise application of therapeutic effort. The final common pathway of this whole circuit is generation of action potential which itself can be modified allowing for additional control. Thus overall, efficacy increases but side effects decrease because of extreme specificity of response.

Ref>
https://www.sciencedirect.com/science/article/pii/S0019483217308131
https://www.americanveterinarian.com/journals/amvet/2018/july2018/electroceuticals-the-wave-of-the-future-is-now