How the brain plays a role in rheumatoid arthritis inflammation

Indigophoton

Indigophoton

Senior Member (Voting Rights)
I thought this was interesting, particularly given Younger's upcoming study on neuroinflammation in ME, and also for the possibility of a future breakthrough in treatments for RA that could potentially be of relevance to ME. Any thoughts, @Jonathan Edwards?
In patients with chronic inflammatory conditions, such as rheumatoid arthritis, there has been limited understanding of how this inflammation affects the brain.

A new study published in Nature Communications examines this issue.

"Rheumatoid arthritis is an inflammatory and autoimmune condition with nasty levels of inflammation that can affect a person's joints and the rest of their body, inducing fatigue, sleep and creating cognitive difficulties," says Andrew Schrepf, Ph.D., a research investigator at Michigan Medicine's Chronic Pain and Fatigue Research Center and one of the lead authors of the study.

"Even though it has been assumed for a long time that the inflammation we see in blood is impacting the brain, up until this study we didn't know precisely where and how those changes in the brain were actually happening."

Schrepf says the effects of inflammation are more understood in short-term illnesses, but the same can't be said for chronic conditions.

"When a person becomes sick with the flu, for example, they begin to show symptoms of the inflammation happening in their body, such as feeling lethargic and being unable to control their body temperature," he says. "We wanted to understand what is happening in conditions where patients have inflammation for weeks, months or years, such as in rheumatoid arthritis."
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Despite progress [in treatment of RA], patients continue to report challenging levels of symptoms such as fatigue and mood dysfunction.

"This intriguing data supports the idea that rheumatoid arthritis inflammation targets the brain and not just the joints," Basu says. "By relating these advanced neuroimaging measures back to the patient experience, we provide evidence that the future targeting of central inflammatory pathways may greatly enhance the quality of life of patients with rheumatoid arthritis and potentially other chronic inflammatory disorders."
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The article, https://medicalxpress.com/news/2018-06-brain-role-rheumatoid-arthritis-inflammation
Abstract
It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.
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The paper, https://www.nature.com/articles/s41467-018-04648-0
 
Indigophoton said:
I thought this was interesting, particularly given Younger's upcoming study on neuroinflammation in ME, and also for the possibility of a future breakthrough in treatments for RA that could potentially be of relevance to ME. Any thoughts, @Jonathan Edwards?
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Complete tripe I am afraid. We know that people with RA feel fatigued when they have inflammation in joints and other tissues like pericardium. We know that is predominantly mediated by TNF and IL-6. If you block the cytokines or remove the B cells that trigger the cytokines to be produced the fatigue goes away completely. I cannot see what different patterns of connectivity can possibly have to do with brain inflammation. Maybe they just think these are pictures of people feeling unwell because of cytokines thinking differently. I am prepared to bet nobody replicates this.

And what is the point? We can deal with fatigue in RA if it is due to inflammation - by treating the inflammation.
 
Jonathan Edwards said:
We know that is predominantly mediated by TNF and IL-6. If you block the cytokines or remove the B cells that trigger the cytokines to be produced the fatigue goes away completely. I cannot see what different patterns of connectivity can possibly have to do with brain inflammation
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I admit to knowing nothing about RA myself, but I'm a bit staggered that the researchers didn't know that - it's obvious when you point it out.

Thanks for the response.
 
nonstopflu said:
@Jonathan Edwards

what's the difference between CIC's and cytokines? don't CIC's cause inflammation, too?
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What are you referring to as CIC's?
If you are meaning immune complexes then circulating immune complexes do not themselves cause inflammation but immune complexes in the extravascular space, which may be derived from circulation, can do, via binding to Ig Fc receptors and stimulating cytokine release. There is a very complicated story involved. I wonder why you ask in this context?
 
Jonathan Edwards said:
What are you referring to as CIC's?
If you are meaning immune complexes then circulating immune complexes do not themselves cause inflammation but immune complexes in the extravascular space, which may be derived from circulation, can do, via binding to Ig Fc receptors and stimulating cytokine release. There is a very complicated story involved. I wonder why you ask in this context?
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the best remedy for pain, stiff joints and brain fog is something called Wobenzyme N. Also, no side effects! (typically, anything that works has bad rebound pain, and/or causes stomach pain.) The literature claims that it breaks down Circulating Immune Complexes, so now I'm trying to understand them to "reverse engineer" what's going on in my body. I'm not sure if CICs are the problems in the first place, so I have to understand what they are better, or what else this supp could be breaking down.

This has really been a miracle for me... If you see the reviews on amazon, 1400+ reviews, 4.3 stars and many ppl w comments similar to mine.. Overall, the supplement I can't live without, and far, far better than any of the rx remedies I've tried.

Ingredients (3 pill dose):
  • Bromelain 135mg
  • Chymotrypsin 3 mg
  • Pancreatin 300 mg
  • Papain 180 mg
  • Rutin 150mg
  • Trypsin 72 mg

Comments:
  • Bromelain & Rutin both help me, but much more mild than when combined into wobie. Vegetarian proteolytic enzymes either do nothing or are mild. Bromelain is the best.
  • Not sure whether pancreatin or trypsin is doing the "heavy lifting" in breaking down CIC's (or if "CICs" are the culprit in the first place). I suspect trypsin is better at this, though, because I've taken a supplement w pancreatin and the effect was mild
  • Not sure if taking this long term is safe, so that's another thing I've got to investigate.
  • I take the "loading dose" which is 15 pills in divided doses. Not sure how long the "loading dose" is meant to be sustained.
 
Sorry @nonstopflu, but this is all pseudoscience - complete nonsense stuff. (Sorry to be blunt but I spent my research career on immune complexes and suchlike and worked out the mechanism of inflammation in RA, which indirectly is why I am here.) Circulating immune complexes do occur in rheumatoid arthritis but there is no reason to think they have anything to do with most other sorts of joint pain. Eating enzymes is not going to touch immune complexes anyway. Science does not work unless you get all the right bits in the right order. Just like a Mercedes car - it does not work unless you put the components in the right places - the immune system is that complicated.
 
The substance @nonstopflu mentions seems like a preparation of things to help with digesting food. I imagine it is possible that for someone who has a problem producing enough of some digestive enzymes they might find it helps improve some symptoms, even if the theory they use to explain this improvement is incorrect.
 
Trish said:
I imagine it is possible that for someone who has a problem producing enough of some digestive enzymes they might find it helps improve some symptoms, even if the theory they use to explain this improvement is incorrect.
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I like to be honest, @Trish, as you know. The chances of anything in this mixture being of any use to pains and brain fog through any specific means are about 0.00001%. The chances that this mixture acts as a placebo are about 99.99999%. For a company to claim that their oral enzyme product breaks up immune complexes is a bit like selling timeshares on Lanzarote that have not been built yet - and never will be.
 
Wobenzyme is used extensively in countries like Germany and some neighbouring countries for inflammation-related problems, for example in helping healing injuries. Just because it is virtually unknown in the UK - where healthcare and NHS is very conservative - doesn't mean it is without merit.
 
Jonathan Edwards said:
I like to be honest, @Trish, as you know.
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Very much appreciated.

I was carefully avoiding the p word. (placebo). I agree I can't see any way improving digestion can influence brain fog or inflammation except perhaps in ensuring a good supply of nutrients if someone has deficiencies. Maybe changing the balance in the gut bacteria that some researchers are suggesting influences health in other ways.
 
LightHurtsME said:
Wobenzyme is used extensively in countries like Germany and some neighbouring countries for inflammation-related problems, for example in helping healing injuries. Just because it is virtually unknown in the UK - where healthcare and NHS is very conservative - doesn't mean it is without merit.
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My comments had nothing to do with being known or unknown or where you live. Injuries have nothing to do with circulating immune complexes either. Germany tends to have a high rate of pseudoscientific alternative therapy use in rheumatology.

And it has nothing to do with me being conservative I think, since I am here because I developed a new treatment that nobody else would take interest in, and showed with double blind controlled trials that it was very effective! I am probably the least conservative rheumatologist in the world. And if you consider rheumatoid arthritis (the disease that does have CIC) it is quite interesting to look at which countries were innovators:

Gold UK
Sulphasalazine UK
Penicillamine France
Methotrexate USA
Anti-TNF UK
Rituximab UK
Anti IL-6 rec Japan, UK

Germany - zilch.
 
Jonathan Edwards said:
And it has nothing to do with me being conservative I think, since I am here because I developed a new treatment that nobody else would take interest in, and showed with double blind controlled trials that it was very effective! I am probably the least conservative rheumatologist in the world.
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Yes, I know who you are and am familiar with your work. And I am eternally grateful that despite how the rituximab trial turned out in Norway, you are still here and supporting us (and I get the impression that you are doing it for the reasons of justice, among other things - which I appreciate even more). I especially value your involvement with regards to taking on PACE and related nonsense, raising awareness among those who matter and can influence things in a positive way for ME sufferers. I hope you don't mind me saying (and without wanting to reveal personal information about myself): I often remind other ME sufferers of your positive involvement in ME matters as a way to motivate fundraising for ME research.

But I have also lived in several countries on more than one continent and in developing countries too and nowhere was healthcare as bad as in the UK. The only thing that the NHS ever got right for me is prescribing antibiotics for a bog standard kidney infection. For a relative of mine, we had a doctor who could not recognise tonsillitis and we had to escalate this to a higher up doctor to get penicillin prescribed for bog standard tonsillitis (who then educated the first doctor in front of us by showing them on my relative what tonsillitis looks like). The incompetence is staggering.

Unfortunately, the opinion about NHS among doctors outside the UK, in Europe, is generally unfavourable, from what I have seen. To quote one doctor who listened to my experiences: "I have always known that UK healthcare is bad but I didn't realise it was this bad. Have these doctors even studied medicine? Do they know that their patients come first?" So I guess I will always differ in opinion on NHS from a lot of people because I have experienced better.

(Hoping I am not taking the thread off-topic too much.)
 
LightHurtsME said:
The incompetence is staggering.

Unfortunately, the opinion about NHS among doctors outside the UK, in Europe, is generally unfavourable, from what I have seen. To quote one doctor who listened to my experiences: "I have always known that UK healthcare is bad but I didn't realise it was this bad. Have these doctors even studied medicine? Do they know that their patients come first?" So I guess I will always differ in opinion on NHS from a lot of people because I have experienced better.
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Yes, and I agree with most of that but it has nothing to do with being conservative. It has to do with with no funding. The expenditure per head on health care in the UK is about 70% of what it is in most other western Europe countries. Since a considerable proportion of health costs are fixed that must mean that a large part of NHS care is hopelessly inadequate. And it is. Because for some reason the UK public do not want to pay for health care - or do not want to elect politicians who will arrange payment.

I keep saying I did;t realise just how bad UK healthcare is. My recent experiences are that it is totally unsafe.

But I don't think that has anything to do with doctors not studying medicine. Over the years I have been regularly to medical conferences and it seems clear to me that UK doctors know at least as much medicine as those from other countries and probably more. What may be different is that they tend not to use unproven treatments because they are less involved in private practice or commercial hospitals. They believe that the patient does come first in the sense of not selling them useless stuff.

The sad thing is that in the last ten years or so bureaucracy and politics has swamped even the good doctors. Quackery has become standard in the NHS in the form of IAPT etc.
 
Having lived in the UK for my first 26 years and Germany for my second 26 years, I can agree with this:

LightHurtsME said:
Unfortunately, the opinion about NHS among doctors outside the UK, in Europe, is generally unfavourable, from what I have seen. To quote one doctor who listened to my experiences: "I have always known that UK healthcare is bad but I didn't realise it was this bad. Have these doctors even studied medicine? Do they know that their patients come first?" So I guess I will always differ in opinion on NHS from a lot of people because I have experienced better.
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I can also agree with this:

Jonathan Edwards said:
Germany tends to have a high rate of pseudoscientific alternative therapy use in rheumatology.
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With the last two words deleted. Whilst I would much rather be ill in Germany and my experience of the health system here is much better than in the UK, German doctors will believe and peddle any old twaddle. The doctor in my village swung a pendulum over my son for allergies and charged my wife 40 euros for private treatment. The only time I've ever insisted on a refund. The doctor in the next village told me 95% of his patients come to him with psychosomatic complaints, then shoved his finger up my arse to check my prostate. Not that I asked him to, I went there to complain about a 6-week headache (the onset of my ME). I haven't been back. Private doctors here set themselves up as an authority on ME and charge a fortune for vitamin B12 injections and other such tosh.

The fact that Wobenzyme is used extensively in countries like Germany doesn't mean a lot. In my experience German doctors and their patients are as susceptible to quackery and pseudoscience as anyone else (especially if it's "natural").

Sorry to be so ranty, but it pisses me off.
 
I think we have to be careful with the word “inflammation”. It seems to have been hyjacked by the snake oil salesmen somewhat.

I see this a lot for aids to digestive conditions where pain is being equated to inflammation ...this is not correct you can have pain without inflammation for a variety of reasons.

This is a marketing trick to add credibility/validation to pain and sell more product.

I’m not trying to invalidate anybodies pain by the way ....just pointing out that there is a lot of unregulated garbage out there when it comes to supplements and ‘natural’ remedies
 
Sly Saint said:
Hema Chaplin, Ailsa Bosworth, Jessica Meehan, Rona Moss-Morris, Heidi Lempp, Sam Norton
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Interesting to see a prominent patient activist taking part in a GIGO study like this.

Th first author is of Cours a health psychologist. I cannot see what psychology has to do with refractory inflammatory disease - other than of course as a term for use in healthcare marketing.
 
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