Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis

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49
I don't understand the tweet. Is Dr. VanElzakker saying that the CRFR2 is ONLY upregulated in the case of LH? This doesn't gel with even a cursory view of googled articles on CRFR2, there are many more recent studies than the one he quotes that link CRFR2 to numerous different things from IBS, delayed stomach emptying, stress modulation, homeostasis, anxiety, it doesn't seem from what I've read that it is only linked to one thing or only linked to LH.
 

nerd

Senior Member
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863

It's funny. One day, I intended to write a post about learned helplessness in ME. Because I think it's an imperative of the condition everywhere patients are bluntly rejected. In my opinion, learned helplessness can be assumed in ME for as long as we're treated how we're treated. Their improvements were mostly on the cognitive and neurological level, who knows how much of our symptoms could be attributed to the common mechanism of learned helplessness, PTSD, chronic pain, chronic physical trauma, and anxiety disorder.
 

nerd

Senior Member
Messages
863
Learnt helplessness is a freeze response in the nervous system

I think the animal model just reflects the same pathophysiological mechanism but not the psychological concept when they use electric shocks. Chronic viral activation, chronic pain, chronic drug use, including SSRIs, everything that chronically disrupts the homeostasis long-term might have the same effects even without psychological involvement. That's why I think that the animal model should not be overinterpreted that it implies that learned helplessness is part of the etiology.

But I think we can imply that learned helplessness becomes a contributing factor once we begin to struggle with how the health systems treat us, when we're left alone. I think this is a valid hypothesis how the health systems might contribute to our conditions getting worse by enhancing at least a downstream effect of the condition that apparently seems to be difficult to reverse.

Most serotonin is made in the intestines. Microbiome dysruption can lead to these symptoms.

Most serotonin is stored and transported in platelets. One valid theory for the pathogenesis of COVID-19 is serotonin intoxication by the destruction of these platelets. Cannabinoids also mess with the serotonin system. I'm not sure if it's part of the etiology but it can certainly contribute to the pathogenesis. I've read many reports about ME starting after cannabinoid or SSRI use. That's why I'm so annoyed that they try SSRIs with Post-COVID patients.

A little history here - s4me was started by a group of members from here who didn't believe in functional medicine, nutrition, microbiome dysruption, Rituximab and a bunch of other things, driven by a few very unpleasant people and decamped to form their own site. I take any of their conclusions with a grain of salt.

And their moderation removes alternative views. I've had my own negative experiences with a double standard, so I left their forum.

At this point lots of us are just looking for a treatment that gives us a better quality of life and a cure seems unlikely. I'm sure many people with MS feel the same. I hope they can find the money to enable a subset or even a handful of people live a better life. Same with Ampligen. Just get it out there.

I couldn't agree more. It might take a long time until we get there, and as I've explained, I think there might also be a feedback loop. Hyperreactivity to stress can reactivate viruses, the viruses might cause PEM, and on and on we go into the rabbit hole.

I wouldn’t read too much into that. They are notoriously pessimistic. Nothing is ever promising In their eyes. This is just a tiny, preliminary study. Bateman wouldn’t waste her time if she saw no promise IMO.

I posted some of my first theories there and some of my positive supplement experiences. There was this pathologist who was very pessimistic with basically everything. I've never read any constrictive or optimistic ideas from him. So I disagreed and explained why I thought that it's still useful to discuss theories even if there no evidence (yet). But disagreeing with him was interpreted as offensive by their moderation. It's like this opinion from a medical professional was seen superior and not to be questioned.
 

Martin aka paused||M.E.

Senior Member
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2,291
It's funny. One day, I intended to write a post about learned helplessness in ME. Because I think it's an imperative of the condition everywhere patients are bluntly rejected. In my opinion, learned helplessness can be assumed in ME for as long as we're treated how we're treated. Their improvements were mostly on the cognitive and neurological level, who knows how much of our symptoms could be attributed to the common mechanism of learned helplessness, PTSD, chronic pain, chronic physical trauma, and anxiety disorder.
Agreed. But energy?
 

Learner1

Senior Member
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Most serotonin is stored and transported in platelets. One valid theory for the pathogenesis of COVID-19 is serotonin intoxication by the destruction of these platelets. Cannabinoids also mess with the serotonin system. I'm not sure if it's part of the etiology but it can certainly contribute to the pathogenesis. I've read many reports about ME starting after cannabinoid or SSRI use. That's why I'm so annoyed that they try SSRIs with Post-COVID patients.
"Gut bacteria also produce hundreds of neurochemicals that the brain uses to regulate basic physiological processes as well as mental processes such as learning, memory and mood. For example, gut bacteria manufacture about 95 percent of the body's supply of serotonin, which influences both mood and GI activity."

https://www.apa.org/monitor/2012/09/gut-feeling
That gut feeling - American Psychological Association
 

nerd

Senior Member
Messages
863
Agreed. But energy?

This seems to be another issue and oxidative stress might be the mediator for it. But the nervous system could theoretically induce it hormonally, immunologically, and via bowel movements.

"Gut bacteria also produce hundreds of neurochemicals that the brain uses to regulate basic physiological processes as well as mental processes such as learning, memory and mood. For example, gut bacteria manufacture about 95 percent of the body's supply of serotonin, which influences both mood and GI activity."

I wasn't writing this to disagree. I just tried to give more alternatives for how it could contribute.
 

nerd

Senior Member
Messages
863
I don't want to bother you. But I'm very much interested in your theory how?

High adrenaline and noradrenaline levels can contribute to more oxidative stress, though it's more likely a response from the autonomic nervous system.

Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome (2018) [10.3389/fendo.2018.00021]

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder defined by ROME IV criteria as pain in the lower abdominal region, which is associated with altered bowel habit or defecation. The underlying mechanism of IBS is not completely understood. IBS seems to be a product of interactions between various factors with genetics, dietary/intestinal microbiota, low-grade inflammation, and stress playing a key role in the pathogenesis of this disease. The crosstalk between the immune system and stress in IBS mechanism is increasingly recognized. Corticotropin-releasing factor (CRF), a major mediator in the stress response, is involved in altered function in GI, including inflammatory processes, colonic transit time, contractile activity, defecation pattern, pain threshold, mucosal secretory function, and barrier functions. This mini review focuses on the recently establish local GI-CRF system, its involvement in modulating the immune response in IBS, and summarizes current IBS animal models and mapping of CRF, CRFR1, and CRFR2 expression in colon tissues. CRF and receptors might be a key molecule involving the immune and movement function via brain–gut axis in IBS.

If you think this theory through, it implies that IBS might just be an early manifestation of CFS/ME. There's no causal treatment for it either.
 

Irat

Senior Member
Messages
288
@nerd ,Yes interupted homeostatis of the nervous System and this feed back loop.
And with this things like accupunture,Brain retraining etc can intervene

"These are all things acupuncture has been shown to be effective for, regardless of what the root cause is. We can use acupuncture to help balance the nervous system and restore the body to homeostasis
Acupuncture points are believed to stimulate the central nervous system. This, in turn, releases chemicals into the muscles, spinal cord, and brain. These biochemical changes may stimulate the body's natural healing abilities and promote physical and emotional well-being."


Here an interview how DNRS works on the cell danger response
https://chriskresser.com/how-to-rewire-your-brain-using-dnrs-with-annie-hopper/


The high adrenaline is this what's killing me.definetely
 
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Martin aka paused||M.E.

Senior Member
Messages
2,291
But it can be tricky,as it is very powerful.i had to start with 2 min.and if a practioner does n t know what he is doing it can go wrong....but it did help me so much,but now I know it would be too strong for me
Yes you I remember that you react very strongly now to any kind of therapy. That's awful.
Did it help you with energy too?
 

Irat

Senior Member
Messages
288
Yes you I remember that you react very strongly now to any kind of therapy. That's awful.
Did it help you with energy too?
You are rather in the camp with no reactions ,lol,so you might be safe......i had a TCM practioner, and in the beginning he did nothing else but to calm my nervous system,for example he said if he would work on my liver for detox it could kill me.so he was veeeeery careful and I trusted him...once a week for 2 months and later ones a months only as it is expensive too.yes sure it did help with energy and later he also worked on my organs ....the first thing that improved was my sleep,
 

Martin aka paused||M.E.

Senior Member
Messages
2,291
@Irat It's always the same with ME... It's unpredictable if it works or makes you worse. For me, it would be hard to obtain acupuncture bc I'm bedridden 24/7. But I know a therapist that does home visits... I just don't know if she is good and after all you said I'd better be careful.
 

Irat

Senior Member
Messages
288
@Irat It's always the same with ME... It's unpredictable if it works or makes you worse. For me, it would be hard to obtain acupuncture bc I'm bedridden 24/7. But I know a therapist that does home visits... I just don't know if she is good and after all you said I'd better be careful.
Yes always unpredictable.with everything...you could write her an email ,explaining,and see how she responses,if she says no problem ,run,lol
 

nerd

Senior Member
Messages
863
And with this things like accupunture,Brain retraining etc can intervene

Here, I would be the one asking for actual evidence that these things can reverse the brain remodeling. It can have a relaxing effect, no doubt, but there's no primary mechanism at these receptors. Any kind of massage might do the same, just my opinion.
 

Irat

Senior Member
Messages
288
Here, I would be the one asking for actual evidence that these things can reverse the brain remodeling. It can have a relaxing effect, no doubt, but there's no primary mechanism at these receptors. Any kind of massage might do the same, just my opinion.
The evidence would be the ppl they have been helped with.....and there are studies who show how acupuncture works on the brain ,pain,sleep,detox,immune system etc its definitely not about calming your brain,and neuroplasticity is also not about calming down,but about remodeling.calming down alone does nothing

but I m tired on talking about this.Everyone can try it themselves,read about it,or contact ppl who have done it .For brain retraining you can find plenty of ppl who done it,with and without success

Don t focus on a cure ,but on improvements .one step at a time.Every tiny relief and progress can be a huge victory in this mess.
 
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