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Sarvaiya: Investigation of the effects of vanilloids in chronic fatigue syndrome

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
If, without ongoing challenge, you can get:

1) Fatigue reducing activity level. (easily measurable - compare activity to unchallenged mice)
2) PEM - again - give them some physical exercise they would normally seek out for reward and see if you get PEM.
3) Sleep dysfunction - again easy.
4) Pain - more problematic.
5) Neurocognitive problems - problems in maze running, and interacting with others.
6) a) POTS, palor, nausea/IBS, urinary frequency
...
Many, or most of these seem measurable in mice.

ME PEM usually has a delay before it appears. Those poor worn out mice would be exhausted after their swim but I bet they arent testing for a worsening in fatigue/malaise 24 hours later then when they first finished their swim.

umm though i guess very hard exercise in one which isnt used to it would in fact cause soreness in anything more the next day when the muscles start hurting due to the lactic buildup.

So how would they distinguish a mouse not wanting to move next day due to the normal affects of too much unused to exercise? from a mouse having actual proper ME/CFS PEM. Even a healthy person if you exercised them extremely hard would be sore next day and not want to move and we know that doesnt mean that person has ME/CFS PEM

I keep thinking I wouldnt be surprised if they didnt test for Neurocog issues either as lots of these crappy research researchers just seem to be too lazy to test for much. Maybe someone should put in an information request exactly what tests they did on the mice to prove they had CFS? I so want to know. or was it just a tired mice study.

Has anyone been able to read this full study to see if it has got the info in it on how they determined the mice had ME/CFS?
 
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RogerBlack

Senior Member
Messages
902
ME PEM usually has a delay before it appears. Those poor worn out mice would be exhausted after their swim but I bet they arent testi
So how would they distinguish a mouse not wanting to move next day due to the normal affects of too much unused to exercise? from a mouse having actual proper ME/CFS PEM. Even a healthy person if you exercised them extremely hard would be sore next day and not want to move and we know that doesnt mean that person has ME/CFS PEM

Quite - this is a ridiculous exercise.
I specifically said above 'If after the end of the challenge' - that is - if after two weeks of doing this, if you leave it a couple of weeks and then test the mice for behaviour then.
They do not apparently do this at all, they do the testing on the same days, so this is an overtraining/stress response not a classic CFS long-lasting system.

https://www.ncbi.nlm.nih.gov/pubmed/19207541 - is another example of this 'model' in the past.
 

Hip

Senior Member
Messages
17,824
Maybe someone should put in an information request exactly what tests they did on the mice to prove they had CFS? I so want to know. or was it just a tired mice study.

All the ME/CFS mouse studies I have seen use the forced swim approach. It's not just the study in question. If you look at this search of PubMed, you'll see what I mean.

That's why we need to develop a decent mouse model of ME/CFS.



I scream with both if I see one run across the floor.

I am the opposite; I think rats, especially little young ones, are incredibly cute, and for me they have the most beautifully sensitive eyes. Our garden backs onto the rear of a few grocery shops, so occasionally you get little young rats from these shops appearing our garden (though mostly they are killed by the poison the local council puts down). To me they seem friendly and curious, but at the same time with a timidity; I find them very cute, and can completely understand why people can develop a rapport with a pet rat.
 

taniaaust1

Senior Member
Messages
13,054
Location
Sth Australia
I am the opposite; I think rats, especially little young ones, are incredibly cute, and for me they have the most beautifully sensitive eyes. Our garden backs onto the rear of a few grocery shops, so occasionally you get little young rats from these shops appearing our garden (though mostly they are killed by the poison the local council puts down). To me they seem friendly and curious, but at the same time with a timidity; I find them very cute, and can completely understand why people can develop a rapport with a pet rat.

actually thinking of it more yeah you are right, some rats do have nice brown eyes where as mice eyes are more beady looking. (my daughter had a pet rat when she was growing up, they are smart and have personallities which remind me of dogs). I dont though tend to be staring into the eyes of wild rats.
 

Little Bluestem

All Good Things Must Come to an End
Messages
4,930
The mouse models of ME/CFS used are quite dubious
How gracious of you. I would call it utterly useless and irredeemable.
But in fact it's something horrible like this:
Ekk! They call that swimming!
i want to know how you get a rat to meet the CCC definition.
Me too.
re: the forced swimming model - they are the model used for research into depression too, as well as other illnesses.
So you force a rodent to swim and it magically develops whatever disorder you wish to research? How convenient!
Imagine if anyone could get CFS by some serious overexertion - even coerced overexertion like this? It would be pretty crowded here by now.
It would include everyone who ever tried to become an Olympic athlete.
 

RogerBlack

Senior Member
Messages
902
It would include everyone who ever tried to become an Olympic athlete.
I still think that looking at hyperendurance athletes after they've just come off a 100 mile run might be interesting.
May they see some transient 'CFS-like' illness - or metabolic signatures thereof?
If we could find cases of CFS which last a couple of weeks (that is - if there was a common trajectory that in some leveled out, and in others lead to rapid recovery) that would be a huge advance.
 

Hip

Senior Member
Messages
17,824
I would call it utterly useless and irredeemable.

It seems to me that the force swim model might possibly have some use in examining PEM from physical exercise. If you look at this PEM busters post (which lists supplements ME/CFS patients on this forum have found mitigate physical PEM), you will see that these same supplements are also useful for improving athletic performance, and most act by reducing lactate levels produced by exercise. So the fact that these supplements work in ME/CFS suggests that athletic endurance in the healthy, and PEM in ME/CFS patients, may be related.

That is to say, it is possible that the physical PEM of ME/CFS in some way resembles the state of physical exhaustion in healthy people (or animals) undertaking exhausting strenuous exercise.


That said, I doubt if this forced swim model captures any of the other characteristics of ME/CFS, such brain fog (concentration and memory problems, etc), orthostatic intolerance, mental PEM, gut symptoms, neuropsychological changes (eg anxiety), muscle pain, headaches, chronic sore throat, etc.
 
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RogerBlack

Senior Member
Messages
902
That is to say, it is possible that the physical PEM of ME/CFS in some way resembles the state of physical exhaustion in healthy people (or animals) undertaking exhausting strenuous exercise.


That said, I doubt if this forced swim model captures any of the other characteristics of ME/CFS, such brain fog (concentration and memory problems, etc), orthostatic intolerance.

Weeeeel.
https://www.ncbi.nlm.nih.gov/pubmed/21892644 - this is an interesting model.
Heavy exercise during thermal shock (running in an insulated suit).
Immediately following the exercise, there were no cognitive deficits.
After 90 minutes, these really become quite notable.
(this makes finding other 'cognition / post exertion' papers hard as it confirms what the first couple I looked at said - that there is no change - because they look too soon for cognitive issues).

https://www.ncbi.nlm.nih.gov/pubmed/19139034
"Significant increases in self-reported balance problems, numbness and tingling were seen for both genders after aerobic exercise."

https://www.ncbi.nlm.nih.gov/pubmed/23932774
"INTERPRETATION:
Fatiguing exercise negatively affected postural control but not proprioception."

At least for some symptoms of ME/CFS, there is a continuum for at least some people (and it's really interesting to me that only some of the firefighters had bad test results post) there may be an overlap.
 

Hip

Senior Member
Messages
17,824
https://www.ncbi.nlm.nih.gov/pubmed/21892644 - this is an interesting model.
Heavy exercise during thermal shock (running in an insulated suit).
Immediately following the exercise, there were no cognitive deficits.
After 90 minutes, these really become quite notable.
(this makes finding other 'cognition / post exertion' papers hard as it confirms what the first couple I looked at said - that there is no change - because they look too soon for cognitive issues).

Interesting finding. I wonder if the cognitive deficits were purely a consequence of the physical exercise, or more due to the overheating of the body, as a result of the exercise being performed in a thermally insulated suit.

But certainly very interesting that there is a delayed effect: where the cognitive deficits only manifest an hour and a half after the exercise.
 

pattismith

Senior Member
Messages
3,932
About TRPV1 receptors...

Involvement of TRPV1 and the efficacy of α-spinasterol on experimental fibromyalgia symptoms in mice

Author links open overlay panelSusana Paula MoreiraFischeraIndiaraBruscoaEvelyne SilvaBrumaMaria Fernanda PessanoFialhoaCamilaCamponogaraaRahisaScusselbRicardo AndrezMachado-de-ÁvilabGabrielaTrevisancSara MarchesanOliveiraa
Show more
https://doi.org/10.1016/j.neuint.2020.104673Get rights and content

Highlights


Reserpine caused nociceptive/depressive-like behaviours without promoting physical alterations.

TRPV1 is involved in the reserpine-induced nociceptive/depressive-like behaviours.

α-spinasterol, a new TRPV1 antagonist, decreased reserpine-induced nociception-depression.

Abstract

Fibromyalgia is characterised mainly by symptoms of chronic widespread pain and comorbidities like depression.

Although these symptoms cause a notable impact on the patient's quality of life, the underlying aetiology and pathophysiology of this disease remain incompletely elucidated.

The transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor that is involved in the development of nociceptive and depressive behaviours, while α-spinasterol, a multitarget TRPV1 antagonist and cyclooxygenase inhibitor, presents antinociceptive and antidepressant effects.

The present study investigated the involvement of the TRPV1 channel and the possible effects of α-spinasterol on nociceptive and depressive-like behaviours in an experimental fibromyalgia model.

The fibromyalgia model was induced with a subcutaneous (s.c.) injection of reserpine (1 mg/kg) once daily for 3 consecutive days in male Swiss mice.

Reserpine administration depleted monoamines and caused mechanical allodynia.

This dysfunction was inhibited by SB-366791 (1 mg/kg, oral route [p.o.]), a selective TRPV1 antagonist, with a maximum inhibition (Imax) of 73.4 ± 15.5%, or by the single or 3-day-repeated administration of α-spinasterol (0.3 mg/kg, p.o.), with an Imax of 72.8 ± 17.8% and 78.9 ± 32.9%, respectively.

SB-366791 also inhibited the increase of the reserpine-induced immobility time, with an Imax of 100%, while α-spinasterol inhibited this parameter with an Imax of 98.2 ± 21.5% and 100%, by single or repeated administration, respectively.

The reserpine-induced mechanical allodynia and the thermal hyperalgesia were abolished by TRPV1-positive fibers desensitization induced by previous resiniferatoxin (RTX) administration.

In summary, the TRPV1 channel is involved in the development and maintenance of nociception and depressive-like behaviours in a fibromyalgia model, while the α-spinasterol has therapeutic potential to treat the pain and depression symptoms in fibromyalgia patients.