Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

nerd

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Authors: Jessica Van Oosterwijck, Uros Marusic, Inge De Wandele, Mira Meeus, Lorna Paul, Luc Lambrecht, Greta Moorkens, Lieven Danneels, Jo Nijs
Published on: September 30, 2021
pmid: 34640544
doi: 10.3390/jcm10194527

Abstract
Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.
 

Pyrrhus

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Thanks for posting!

This paper is by Jo Nijs, a researcher who has done some good research in ME as well as some questionable research.

In response to:
Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients.
I would say that the published body of evidence makes it abundantly clear that autonomic nervous system (ANS) dysfunction (AKA dysautonomia) is indeed a central feature of ME. I consider this to be a firm conclusion. A foregone conclusion, even.


But here's the take home message:
Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS.

(I would like to point out that the autonomic nervous system contains perhaps dozens of pre-programmed physiological responses, so it seems a bit outdated to try to classify autonomic responses as simply either sympathetic or parasympathetic. However, from a purely anatomical perspective, the sympathetic-parasympathetic distinction still holds clear relevance in the peripheral nervous system.)
 

Oliver3

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Added to that, I've often wondered if say 6 months of some kind of anesthesia that allowsp sone healing to take place could be a protocol ? I know it sounds crazy, but I once slept at a friend's house and I had a headache. She gave me , what I thought were paracetamol, but turned out to be hardcore post surgery painkillers.
I didn't feel drugged. Just safe and fantastic.
Could snthg like that be a protocol that could be monitored and let out poor bodies rest a while
 

nerd

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Added to that, I've often wondered if say 6 months of some kind of anesthesia that allows some healing to take place could be a protocol?
GABA receptor function in the parasympathetic ganglia (1994) [pmid: 7752515]

Kataoka et al. said:
The criteria required to establish gamma-aminobutyric acid (GABA) as a neurotransmitter have been fulfilled in the enteric nervous system of the mammalian intestine. In the intestine, GABA-A receptors are located on somato-dendritic regions of the postganglionic cholinergic neurons and mediate the release of acetylcholine (ACh). GABA-B receptors are located on nerve terminals of the cholinergic neurons and mediate inhibition of nerve-stimulated release of ACh. In the urinary bladder, GABA is possibly a noncholinergic, nonadrenergic inhibitory neurotransmitter. Both GABA-A and GABA-B receptors seem to be present in the parasympathetic ganglia and mediate inhibition of ACh release from the cholinergic neurons. Thus, the functional property of GABA-A receptor is different between the intestine and urinary bladder. GABA-A receptors are also located on the GABAergic nerve terminals as an autoreceptor, and mediate inhibition of GABA release both in the intestine and urinary bladder.
My understanding of sympathetic vs. parasympathetic activation is that it is mediated by glutamate and GABA receptors as the respective players. It's consistent with different kinds of evidence on glutamatergic and GABAergic activity in ME.

A common group of anesthetics does exactly that. They upregulate GABAergic activity either by agonism or by modulation of the receptors. One theory for the ME pathogenesis is a shift in the homeostasis that prevents sufficient GABAergic potential. Another theory is that the metabolism prevents sufficient GABA from being converted.

There was a recent post on which antidepressants might be viable for ME (other than SSRIs). Interestingly, most of the alternatives interact with GABA receptors in one way or another.

Assuming these theories are applicable, one of the challenges of medication is a habituation effect that desensitizes receptors or makes the homeostasis dependant on a drug.
 

Oliver3

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@Oliver3 Psylocibin is being used to treat depression and PTSD. I'm not sure how that relates to parasympathetic vs sympathetic activation.

Here's a nice article: https://www.nature.com/articles/d41586-021-00187-9
Thank you. I tried to get on that trial but when they found out I had m.e. they said it would skew the results for PTSD/ depression.
I think there may be some link.
Years and years ago I did gestalt therapy and it's the only time anything worked for that horrible adrenaline life.
I'm not somatising our illness. I don't see the difference between mind and body anyway but we seem predisposed to PTSD.
What transpired was I felt completely unsafe in my world at a deep level. When I found some human safety, that PTSD just went...I mean it was incredible. It was someone giving me that space to be myself. I'd been holding in this massive trauma from my youth, mixed with those rcccx genes n viruses. But at the time, the release of that emotional repression was better than any drug.
Problem was, with my sensitivities, I couldn't live in that state outside that safe zone.
With psychedelic s, I believe you can constantly shift that safety and trust in the world through shaking up these well worn circuits. The BBC documentary of that Imperial college trial was moving. People who were just in that unremitting hell, suddenly were...normal!!!
But it's a scary thing to do.
Also I think, this unaddressed PTSD has sent us biologically to a place that is hard to come back from.
But I do remember Ron saying that in Whitney's class, there was a girl with cfs wh recovered by an almost insane attention to detail on heart beats feeding etc.
Much easier when you're in your twenties tho.
To be clear, i think m.e. is a connective tissue disorder, that presidposes to sensitivity, PTSD, virus growth and autoimmunity and if course the trap.
But if psylocibin could get rid of some of or all of that PTSD element, then other parts may calm down. And take us further away from being severe.
Just an idea...I often yearn for just a feeling of will being , as we all do I'm sure, and either anesthetic or some kind of plant based psychedelic may help with the activation
 

Oliver3

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GABA receptor function in the parasympathetic ganglia (1994) [pmid: 7752515]



My understanding of sympathetic vs. parasympathetic activation is that it is mediated by glutamate and GABA receptors as the respective players. It's consistent with different kinds of evidence on glutamatergic and GABAergic activity in ME.

A common group of anesthetics does exactly that. They upregulate GABAergic activity either by agonism or by modulation of the receptors. One theory for the ME pathogenesis is a shift in the homeostasis that prevents sufficient GABAergic potential. Another theory is that the metabolism prevents sufficient GABA from being converted.

There was a recent post on which antidepressants might be viable for ME (other than SSRIs). Interestingly, most of the alternatives interact with GABA receptors in one way or another.

Assuming these theories are applicable, one of the challenges of medication is a habituation effect that desensitizes receptors or makes the homeostasis dependant on a drug.
Habituation is deffo a problem, but perhaps there could be a way of surfing that wave.
I mean two days a week of much less of the hell feeling would be nice.
The psylocibin thing suggests there is a permanent change to openness which is the opposite of sympathetic dominance.
When I first started taking diaezepam, my pots went, I could walk a bit..say twenty minutes.
Like you say, you habituate, but just for quality of life, I'm suprised there's no protocol where we can have a weekend off m.e. with a drug
 

Oliver3

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GABA receptor function in the parasympathetic ganglia (1994) [pmid: 7752515]



My understanding of sympathetic vs. parasympathetic activation is that it is mediated by glutamate and GABA receptors as the respective players. It's consistent with different kinds of evidence on glutamatergic and GABAergic activity in ME.

A common group of anesthetics does exactly that. They upregulate GABAergic activity either by agonism or by modulation of the receptors. One theory for the ME pathogenesis is a shift in the homeostasis that prevents sufficient GABAergic potential. Another theory is that the metabolism prevents sufficient GABA from being converted.

There was a recent post on which antidepressants might be viable for ME (other than SSRIs). Interestingly, most of the alternatives interact with GABA receptors in one way or another.

Assuming these theories are applicable, one of the challenges of medication is a habituation effect that desensitizes receptors or makes the homeostasis dependant on a drug.
Psylocibin also creates neuron genesis.
I think I'm gonna take the plunge.
Will report back, maybe from the psyche ward!
But at this point anything seems worth a go
 

SWAlexander

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Thank you. I tried to get on that trial but when they found out I had m.e. they said it would skew the results for PTSD/ depression.
I think there may be some link.
Years and years ago I did gestalt therapy and it's the only time anything worked for that horrible adrenaline life.
I'm not somatising our illness. I don't see the difference between mind and body anyway but we seem predisposed to PTSD.
What transpired was I felt completely unsafe in my world at a deep level. When I found some human safety, that PTSD just went...I mean it was incredible. It was someone giving me that space to be myself. I'd been holding in this massive trauma from my youth, mixed with those rcccx genes n viruses. But at the time, the release of that emotional repression was better than any drug.
Problem was, with my sensitivities, I couldn't live in that state outside that safe zone.
With psychedelic s, I believe you can constantly shift that safety and trust in the world through shaking up these well worn circuits. The BBC documentary of that Imperial college trial was moving. People who were just in that unremitting hell, suddenly were...normal!!!
But it's a scary thing to do.
Also I think, this unaddressed PTSD has sent us biologically to a place that is hard to come back from.
But I do remember Ron saying that in Whitney's class, there was a girl with cfs wh recovered by an almost insane attention to detail on heart beats feeding etc.
Much easier when you're in your twenties tho.
To be clear, i think m.e. is a connective tissue disorder, that presidposes to sensitivity, PTSD, virus growth and autoimmunity and if course the trap.
But if psylocibin could get rid of some of or all of that PTSD element, then other parts may calm down. And take us further away from being severe.
Just an idea...I often yearn for just a feeling of will being , as we all do I'm sure, and either anesthetic or some kind of plant based psychedelic may help with the activation
PTSD is the big reason I´m “pushing” to include the endocrinal system in ME/CFS research.
From 1994 to 2016 I led the organization “Adults abused in Childhood worldwide” and almost all displayed symptoms we call today ME/CFS. This was the reason I asked Bill Clinton for research money in 2000 and he made $10 million for Safe Start grants available: http://boxbook.com/letters/letter-from-bill-clinton/

Maybe you like to read: “The Biological Effects of Childhood Trauma” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968319/

The most severe symptoms were expressed by people with sexual abuse:
“Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment”: https://www.nature.com/articles/tp201160
Also:
“Childhood adversity increases risk for depression and chronic inflammation”: https://www.sciencedaily.com/releases/2012/07/120703133721.htm
 
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