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

[VisualEffect]

I googled some info about CRHR2 and I decided to post it here, because I found it really interesting.

CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension

Interestingly, CRH-producing neurons in the PVN (paraventricular nucleus of the hypothalamus) also project to the rostral ventrolateral medulla and the nucleus of the solitary tract (NTS), where they may regulate sympathetic activity and blood pressure.

Both CRHR1 and CRHR2 are expressed in the NTS, a key nucleus in integrating the peripheral chemoreflex and baroreflex inputs and regulating the sympathetic outflow.

So CRHR2 upregulation in brainstem NTS region can explain orthostatic intolerance?

In my opinion Cortene's hypothesis fits ME/CFS accurately, because the disease starts after some major stressor to the body. Maybe ME/CFS trigger shocks our stress response system via immune, endocrine or metabolic challenge and leaves critical receptor upregulated somewhere in the brain. So if our ANS is not irreversibly ruined, but only locked in dysfunctional state, maybe this disease can be fixed?

 

[perrier]

I googled some info about CRHR2 and I decided to post it here, because I found it really interesting.

CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension


So CRHR2 upregulation in brainstem NTS region can explain orthostatic intolerance?

In my opinion Cortene's hypothesis fits ME/CFS accurately, because the disease starts after some major stressor to the body. Maybe ME/CFS trigger shocks our stress response system via immune, endocrine or metabolic challenge and leaves critical receptor upregulated somewhere in the brain. So if our ANS is not irreversibly ruined, but only locked in dysfunctional state, maybe this disease can be fixed?

any updates on Cortene???

 

[Learner1]

I googled some info about CRHR2 and I decided to post it here, because I found it really interesting.

CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension


So CRHR2 upregulation in brainstem NTS region can explain orthostatic intolerance?

In my opinion Cortene's hypothesis fits ME/CFS accurately, because the disease starts after some major stressor to the body. Maybe ME/CFS trigger shocks our stress response system via immune, endocrine or metabolic challenge and leaves critical receptor upregulated somewhere in the brain. So if our ANS is not irreversibly ruined, but only locked in dysfunctional state, maybe this disease can be fixed?

I think my dysautonomia is caused by autoimmune antibodies. So, I don't think this theory applies. Most dysautonomia is known to be autoimmune these days, though there are some that are caused by thiamine deficiency. Maybe you have a third theory.

 

[VisualEffect]

any updates on Cortene???

I don't know, but I really want to hear anything about Cortene at least in 2022.

I think my dysautonomia is caused by autoimmune antibodies. So, I don't think this theory applies. Most dysautonomia is known to be autoimmune these days, though there are some that are caused by thiamine deficiency. Maybe you have a third theory.

Every complex mechanism can broke itself when something unintentionally bad happens, at certain time and given circumstances. I don't know anything about autoimmune process, and thiamine defiency is very rare, but since our ANS is very complex, I think it's possible to break it with some external stimulus, unfortunately.

Corticotropin-releasing hormone projections from the paraventricular nucleus of the hypothalamus to the nucleus of the solitary tract increase blood pressure

The nucleus of the solitary tract (NTS) is a key region in the brain stem that integrates arterial baroreceptor and chemoreceptor inputs and regulates sympathetic outflow. Caudal regions of NTS express low levels of corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1) but high levels of CRH type 2 receptors (CRHR2) (Wang et al. 2018).

If that's true, any drug that can target CRHR2 is worth trying in ME/CFS patients, because many patients have reduced cerebral blood flow and sympathetic predominance. I wonder if there is any ME/CFS patients without any signs of orthostatic intolerance, only cognitive impairment?

 

[lenora]

Hello @Martin aka paused||M.E. .......Congratulations on what may be a possible solution for at least some of your problems. Has anyone gone beyond the 28 days mentioned or is that the maximum at this time?

Well, doesn't matter because you've helped prove that it can be done. What a nice gift for the new year.

Yes, I think anxiety/panic attacks are common in our "club." I know that had a pituitary tumor long before anything else was found. For years it was controlled by the drug, bromocriptine, and then went away on its own. I consider myself fortunate....but it didn't mean an end to all of the panic problems. I'm now on meds for them, but this has been over a very long period of time. Yes, these things have truly happened to me....I didn't wait in line for them, but clues were everywhere. No one could possibly have put the entire puzzle together...at least then.

So my heartiest congrats to you. I really hope it translates into some serious good news for you and I do wish you well. Yours, Lenora.

 

[livinglighter]

If that's true, any drug that can target CRHR2 is worth trying in ME/CFS patients because many patients have reduced cerebral blood flow and sympathetic predominance. I wonder if there are any ME/CFS patients without any signs of orthostatic intolerance, only cognitive impairment?

When I experienced remission in 2019, I only had cognitive impairment as a symptom (no more fatigue, crashes, PEM, sleep disturbance, rapid weight gain, increased hunger, hair loss, early morning brain fog, red eyes). I believe I went into remission due to accidentally taking a high enough dose of vitamin D, which has been shown to modulate both the innate and adaptive immune responses.

https://www.frontiersin.org/research-topics/9039/immune-modulatory-effects-of-vitamin-d
https://www.frontiersin.org/articles/10.3389/fimmu.2020.566781/full
https://www.frontiersin.org/articles/10.3389/fimmu.2015.00513/full#:~:text=management of SLE.-,Conclusion,thus contribute to autoimmune diseases.

I could tell I was 99% back to normal, but my pre-illness level of cognition hadn't returned.

Based on all the theories and some information relayed back from specialists. I think we do all vary in subsets, unlike post covid suffers, who are all post-viral sufferers. When considering my own worst symptoms (cognitive impairment/sensory disturbances) plus relapsing and remitting pattern of symptoms. I think Dr Hyde's theory explains that I may have some form of post-traumatic brain injury following the acute infection I suffered, which is further compounded by symptoms caused by a hyperimmune response.

I also think ME results from a significant stressor to the body. In most cases, it is an infection but can also follow stressors such as vaccines, pregnancy/childbirth, surgery, cancer treatment, injury, etc. I lean towards the explanation of a hyperimmune response perpetuating the illness. I think if the response is dampened down or turned off, as it may have been in my case, the debilitating symptoms will stop.

Neurologists seeing long covid patients with neurological symptoms are already discussing/using available drugs to turn off the hyperimmune response.

https://thephysiciansclinic.co.uk/n...-discusses-neurological-manifestations-covid/

 

[perrier]

When I experienced remission in 2019, I only had cognitive impairment as a symptom (no more fatigue, crashes, PEM, sleep disturbance, rapid weight gain, increased hunger, hair loss, early morning brain fog, red eyes). I believe I went into remission due to accidentally taking a high enough dose of vitamin D, which has been shown to modulate both the innate and adaptive immune responses.

https://www.frontiersin.org/research-topics/9039/immune-modulatory-effects-of-vitamin-d
https://www.frontiersin.org/articles/10.3389/fimmu.2020.566781/full
https://www.frontiersin.org/articles/10.3389/fimmu.2015.00513/full#:~:text=management of SLE.-,Conclusion,thus contribute to autoimmune diseases.

I could tell I was 99% back to normal, but my pre-illness level of cognition hadn't returned.

Based on all the theories and some information relayed back from specialists. I think we do all vary in subsets, unlike post covid suffers, who are all post-viral sufferers. When considering my own worst symptoms (cognitive impairment/sensory disturbances) plus relapsing and remitting pattern of symptoms. I think Dr Hyde's theory explains that I may have some form of post-traumatic brain injury following the acute infection I suffered, which is further compounded by symptoms caused by a hyperimmune response.

I also think ME results from a significant stressor to the body. In most cases, it is an infection but can also follow stressors such as vaccines, pregnancy/childbirth, surgery, cancer treatment, injury, etc. I lean towards the explanation of a hyperimmune response perpetuating the illness. I think if the response is dampened down or turned off, as it may have been in my case, the debilitating symptoms will stop.

Neurologists seeing long covid patients with neurological symptoms are already discussing/using available drugs to turn off the hyperimmune response.

https://thephysiciansclinic.co.uk/n...-discusses-neurological-manifestations-covid/

If this is the probably case; are there CFS/ME researchers on this? Any updated, by the way, from any ME research. Very quiet.

 

[lenora]

This is possible b/c one only has to think of surgery in the same league as brain injury. Both are shock to the brain in one way or another. Injury would simply be another way of describing it. Yours, Lenora

 

[livinglighter]

If this is the probably case; are there CFS/ME researchers on this? Any updated, by the way, from any ME research. Very quiet.

Unfortunately, due to cognitive issues I haven't been able to read lots of research or keep up to date with ongoing studies. Hopefully the forum members who are up to speed will advise.

 

[livinglighter]

This is possible b/c one only has to think of surgery in the same league as brain injury. Both are shock to the brain in one way or another. Injury would simply be another way of describing it. Yours, Lenora

The "stress response" referred to in ME/CFS is an immune function. It is not mental stress (many assume it means a respnse to mental stress). The stress response takes place when any stressor is applied. It even happens when a healthy body exercises aswell - it just happens as its supposed to because it's not overactive.
It's that response that causes you to feel generally off and achy if you over do it in the gym, so you rest instead doing more. The stress response is abnormal in ME/CFS and is said to result in PEM.

 

[Consul]

Apparently part of Cortene inc´s team:

https://corteneinc.com/cort-johnson/

 

[livinglighter]

Dr J Goldstein also attributed the limbic system as being the cause of ME/CFS very early on. He has a few books covering his limbic theory and how he treated patients. His books are the last I’m going to read on the subject as I am convinced the PNEI model explains ME. The PNI model I posted some time ago was the one that was used to explain the current known pathology of ME/CFS to me under the NHS. Can they say it’s what they know if it is merely what they think?

Like AIDS and Cancer currently there is no cure but symptoms can be isolated and treated in pathological isolation.

 

[VisualEffect]

Cardiovascular functions of central corticotropin-releasing factor related peptides system
If everything written in this paper is well known facts, and not some speculations. I wonder why it has so little interest from ME/CFS researchers?

 

[Hoosierfans]

Anything ever happen to Cortene? Google isn’t showing anything. @Cort??