Stimulation of the Vagus Nerve: 'Nerve Hack' Offers Arthritis Sufferers Hope

[ruben]

Interesting article today on Sky news about a new treatment from Holland for arthritis and suggestions it could be used for all kinds of other conditions. Just thought I'd highlight it.

 

[Bob]

It's vagus nerve stimulation to treat rheumatoid arthritis, in a small study of 20 patients showing a 50% response rate:

'Nerve Hack' Offers Arthritis Sufferers Hope
http://news.sky.com/story/1396464/nerve-hack-offers-arthritis-sufferers-hope

"We may be able to achieve remission in 20% to 30% of patients, which would be a huge step forward in the treatment of rheumatoid arthritis."

Doctors hope the nerve stimulator could be widely used within 10 years. But they admit they don't yet fully understand how it has such a powerful effect.

The implant stimulates the vagus nerve, which connects the brain to the major organs and is responsible for many 'automatic' body functions such as breathing and heart rate.

By firing impulses for just three minutes a day, scientists were able to reduce the activity of the spleen, a key organ in the immune system.

Within a matter of days the organ produced fewer chemicals and other immune cells that cause the abnormal inflammation in the joints of people with rheumatoid arthritis.

 

[Sherlock]

Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504833/

Here, we show that vagus nerve stimulation during endotoxemia specifically attenuates TNF production by spleen macrophages

During infection, homeostasis is significantly perturbed, in part, because cells of the immune system release soluble factors that act on the brain and other tissues to mediate physiological responses. For example, cytokines like TNF, IL-1β, and other soluble factors mediate fever, anorexia, shock, and tissue injury (1). Although the effect of cytokines on the nervous system has been known for decades, only recently has it become evident that the autonomic nervous system, in turn, regulates cytokine production through neural pathways. We have previously shown that efferent vagus nerve signals regulate cytokine production through the nicotinic acetylcholine receptor subunit α7, a mechanism termed “the cholinergic antiinflammatory pathway.”

In the course of studying the functional and anatomical basis of cholinergic regulation of cytokines in disease models, we discovered that the spleen is required for the cytokine regulatory effect of vagus nerve stimulation

 

[msf]

I think this could be a very exciting development. I definitely perked my interest (which is unusual for Sky News). It seems to me that, if the vagus nerve hypothesis that Cort wrote about on Phoenix Rising is true, and if other treatments for Rheumatoid Arthritis that affect the immune system, like Rituximab, also work in some ME patients, then there is a chance that this will also work for some. The article mentioned that they try it with other disorders too, such as diabetes, so it seems that it might have a more general application than has been shown so far.

I would be interested in Prof. Edward's (or someone else who understands the immune system and Rheumatoid Arthritis) take on how this might work in RA, and whether it might prove effective in some people with ME.

I would just like to point out that I do not usually get excited about new medical developments, and this one will obviously not be available for a long time (a doctor on the program suggested a timeframe of around 10 years), but if it proves effective for some patients then it would be a very elegant solution to their problems (assuming the side effects aren't too bad).

 

[Sherlock]

efferent vagus nerve signals regulate cytokine production through the nicotinic acetylcholine receptor subunit α7, a mechanism termed “the cholinergic antiinflammatory pathway.”

which leads to

Nicotine, a major component of tobacco smoke, has been shown to strongly modify the inflammatory response both in vitro and in vivo [5]–[8]. Its anti-inflammatory action, like that of the endogenous neurotransmitter ACh, is due to its binding to and activation of α7 nicotinic acetylcholine receptors (α7 nAChRs) on resident macrophages under the control of the ‘cholinergic anti-inflammatory pathway’ (CAP) [5], [6], [9], [10]. This anti-inflammatory pathway, first identified by the Tracey group, constitutes the efferent arm of a vagal nerve circuit directly linked to the immune system. The physiological activation of CAP is critical to ensure the appropriate magnitude of the inflammatory response to an infection or injury since it culminates in T cell release of ACh and the interaction of the neurotransmitter with α7 nAChRs on resident macrophages in the spleen, thereby inhibiting pro-inflammatory cytokine production by these macrophages

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178160/

 

[Sasha]

Seen this, @Jonathan Edwards?

 

[Sherlock]

this one will obviously not be available for a long time (a doctor on the program suggested a timeframe of around 10 years),

Yes, but that's for the expensive and profitable electronic device being developed by Pharma. That doesn't mean there are not cheaper and readily available means. Just thinking out loud: maybe shiatsu, maybe the electro-stimulators that are sold for abdominal muscle development, maybe nicotine.

 

[msf]

Hmm, in the article they said that it was twisted around the vagus nerve, so it would be difficult to an effect that was that specific, assuming that is that is has to be specific.

 

[Sherlock]

Poking around, I see diaphragmatic breathing being recommended to stimulate the vagus nerve.

 

[Jonathan Edwards]

Seen this, @Jonathan Edwards?

I think I would like to see some data, and information about trial design. I find it very hard to see why stimulating the vagus nerve should help RA - and it seems the authors have no idea either. I don't think I will be holding my breath on this one.

 

[Sherlock]

The idea seems to be that as macrophages pass through the spleen they get exposed to regulatory chemicals which are secreted by nerve ends which are controlled by the vagus nerve. The chemicals tell the macrophages to not produce TNF etc

http://brainimmune.com/role-of-the-vagus-nerve-at-the-neural-immune-interface/

Various animal studies are cited. I suppose it makes sense that the CNS can influence immunity. when you see the bear, the body gets reading for injury and infection.

 

[Sherlock]

High fat diet stimulates vagus nerve and downregulates inflammation?


Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213207/

Based on our findings, high-fat enteral nutrition is potentially therapeutic in various inflammatory disorders such as sepsis and inflammatory bowel disease (IBD) characterized by an inflammatory response in which TNF-α is prominent and intestinal barrier function is impaired. In light of this, a fasted state could be a risk factor for developing a potentially lethal inflammatory response after trauma or injury.

the high-fat liquid enteral diet contained 6.9% (energy %) proteins, 40.9% carbohydrates, and 52.2% fat... The lipid source was vegetable oil with a fatty acid composition of 8.1% saturated fatty acids; 58.9% monounsaturated fatty acids, of which oleic acid was the main source (57.4%); 28.2% consisted of polyunsaturated fatty acids, of which linoleic acid was the main source (23%);

sounds similar to canola - I haven't seen other fats tried (e.g. olive oil has more SFA than PUFA) .

Vagotomy blunts the inhibitory effect of high-fat enteral nutrition on the inflammatory response and preserves gut barrier function.

 

[Sherlock]

Help for leaky gut?


Stimulating the Central Nervous System to Prevent Intestinal Dysfunction After Traumatic Brain Injury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251579/

Traumatic brain injury (TBI) causes gastrointestinal dysfunction and increased intestinal permeability. Regulation of the gut barrier may involve the central nervous system. We hypothesize that vagal nerve stimulation prevents an increase in intestinal permeability after TBI.

 

[garcia]

GSK, which funded the study as part of its £32m investment in the field, said that it hopes to develop the device further so that it could be used for a range of chronic diseases that may benefit from electrical nerve stimulation.

“We believe that one day, tiny devices smaller than grains of rice could be used to restore health in a range of chronic diseases centred on organs and biological functions,” a spokesman said.

http://www.independent.co.uk/life-s...ts-leave-some-patients-pain-free-9941001.html

 

[natasa778]

From the article

“Even in patients who have failed everything, including the most modern pharmaceuticals, we have seen a clear trend of improvement,” Professor Tak told Sky News.

TV interview with Dr Kevin Tracey, very interesting. Gives details in history of the device, how it differs from VNS used in epilepsy etc. Exciting.

http://www.huffingtonpost.com/2014/05/30/nerve-stimulator-arthritis-treatment_n_5420248.html

 

[Sherlock]

who had been quite disfigured and barely able to leave his room for years now functioning fine, running around playing with his daughter.

Did the gnarled nature of the fingers regress any?

 

[natasa778]

I couldn't find info on that @Sherlock here is the most detailed report I could find:

Eight weeks after his surgery, this first patient returned to work, performed manual labor, and drove a delivery truck. When asked about how he felt before and after the surgery, he made it very clear that the vagus nerve stimulator therapy had alleviated the severe pain in his joints. A review of his laboratory test results indicated that his serum levels of CRP, a marker of inflammation that is often elevated in arthritis patients, had fallen from an abnormally high value (more than 20 milligrams per liter), to a normal level (1.2 milligrams per liter). His quality-of-life measures and the number of joints that were swollen, painful, and tender were all significantly improved. His face wore an expression of unbridled joy, gratitude, and relief. ...

www.dana.org/Cerebrum/2012/A_New_Approach_to_Rheumatoid_Arthritis__Treating_Inflammation_with_Computerized_Nerve_Stimulation/

 

[Sherlock]

...and some of the inevitable complexity:
"Vagus Nerve Infection in Chronic Fatigue Syndrome"
http://chronicfatigue.about.com/b/2013/07/10/vagus-nerve-infection-chronic-fatigue-syndrome.htm

A new hypothesis suggests that the ongoing immune response of chronic fatigue syndrome (ME/CFS) may be the result of infection of the vagus nerve.

A lot of research has focused on finding viral or bacterial agents that lead to ME/CFS, but no clear, universal culprit has been found. This hypothesis offers evidence supporting the idea that any vague nerve infection could result in ME/CFS.

--------------------

(Plus, I wonder if people with vasovagal syncopy or neuro mediated hypotension should avoid this altogether.)

 

[kangaSue]

Electrocore Medical make a portable vagus nerve stimulator that is undergoing several clinical trials
http://www.electrocoremedical.com
http://www.faqs.org/patents/app/20130131753