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

Discussion in 'Latest ME/CFS Research' started by mango, Oct 3, 2016.

  1. mango

    mango Senior Member

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    Investigation of the effects of vanilloids in chronic fatigue syndrome

    Kuldeep Sarvaiya, Sunita Goswami

    Department of Pharmacology, L.M. College of Pharmacy, Ahmedabad, 380009 Gujarat, India

    Brain Research Bulletin Volume 127, October 2016, Pages 187–194

    Highlights

    • The chronic fatigue syndrome was produced using forced swim model for 21 days.
    • Vanilloid receptor modulators (Agonist & Antagonist) were used to prevent/improve symptoms of chronic fatigue syndrome.
    • Blocking of vanilloid receptors was found to be one of reason to improve symptoms.
    • The agonist capsaicin showed partial antagonism and showed effects same as antagonist due to desensitization of receptors.

    Abstract


    Aim of the study
    To assess the effectiveness of TRPV1 modulators in animal model of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral activity of TRPV1 modulators.

    Material and methods
    CFS was induced by forcing the rats to swim for 10 min for 21 consecutive days. The rats were treated with capsaicin (TRPV1 agonist, 2.5 mg/kg) and n-tert-butylcyclohexanol (TRPV1 antagonist, 10 mg/kg) for 21 days 30 min before the exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility time, grip strength, locomotor activity, and anxiety level using Rota rod, Actophotometer, and Elevated plus maze model respectively. The other parameters include Plasma corticosterone, adrenal gland and spleen weight, complete blood count, blood urea niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and reduced glutathione (GSH).

    Results and discussion
    TRPV1 modulators reversed (p < 0.05) the increase in immobility period, anxiety, spleen weight, BUN and LDH levels, and MDA levels along with decrease in grip strength, locomotor activity, plasma corticosterone, adrenal gland weight, catalase, and GSH. There was also significant increase in total WBC count when compared with the disease control group. The reversal was attributed to modulation of HPA axis, oxidative stress, anaerobic respiration product, muscle degradation product.

    Conclusion
    The present study reveals the effectiveness of n-tert-butylcyclohexanol and capsaicin against chronic fatigue syndrome. The mechanism of action can be attributed to inhibition of TRPV1 channel and thereby modulating pain perception, neuroendocrine function, oxidative stress and immune function.

    Keywords
    Chronic fatigue syndrome; Fatigue; TRPV1 channel; Vanilloids; Forced swimming test

    http://www.sciencedirect.com/science/article/pii/S0361923016302994
     
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  2. mango

    mango Senior Member

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    My heart breaks into a million pieces for those poor wee rats... :cry::cry::cry:
     
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  3. hixxy

    hixxy Senior Member

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    Hrmmm. I wonder if this mouse model is really ME/CFS? I'd love to see more research into the TRP channels, in particular TRPV1 and TRPA1, but this doesn't really seem like the way to go.
     
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  4. Hip

    Hip Senior Member

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    The mouse models of ME/CFS used are quite dubious: they usually just force the mice to do lots of exercise so that they are knackered, and then just assume that their exhausted state is the same as the ME/CFS state.
     
  5. hixxy

    hixxy Senior Member

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    Yeah. Seems to make the research quite worthless really.
     
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  6. Hip

    Hip Senior Member

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    @hixxy
    When I learnt that Dr Chia found many of his ME/CFS patients developed ME/CFS as a result of being given corticosteroids during an acute enterovirus infection (see here), and that an acute enterovirus infection + corticosteroids was almost a recipe for creating ME/CFS, it occurred to me that you might use this same recipe to try to create real ME/CFS in mice.

    Mice get infected with the same coxsackievirus B infections that humans do, so my guess is that if you infected a mouse with coxsackievirus B, and during the acute state of the infection administered corticosteroids, that may well create genuine ME/CFS disease in the mouse.

    That would then give you a fantastic murine model of ME/CFS to work with, which could really push ME/CFS research forward (eg, you could do lots of mouse brain autopsies, do vagus nerve autopsies, etc etc).
     
    Last edited: Oct 3, 2016
  7. hixxy

    hixxy Senior Member

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    Poor mice. My desire to see more quality ME/CFS research is larger than my empathy for lab mice though.
     
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  8. Hip

    Hip Senior Member

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    Chronically fatigued mice would probably be better off than their human ME/CFS counterparts: they wouldn't have to put up with all that biopsychosocial crap that we do!
     
  9. RogerBlack

    RogerBlack Senior Member

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    This is clearly a biopsychosocial result.
    The mice were fed large amounts of capsaicin, distracting them from their illness behaviour and catastrophising by the intervention of their burning anuses.

    More seriously.
    2.5mg/kg is 250mg for a 100kg adult.
    A Habanero chilie has a scoville rating of about 100K.
    This is six or so milligrams of capsaicin per kilo of chilie.
    So, it's equivalent to a human eating about forty kilos of 'hot' raw chilie - fresh,or about two of the world record chili.


    I note https://www.ncbi.nlm.nih.gov/pubmed/22842953 - which is a study on FM on capsaicin - seems to be .075% cream applied to sore areas - but I can't find dosages.

    If the skin area correction mentioned below is correct, then a half a pound of theworlds hottest pepper, or only three kilos of habanero.
     
    Last edited: Oct 4, 2016
  10. Snow Leopard

    Snow Leopard Hibernating

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    More useless torturing of rats.
     
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  11. Hip

    Hip Senior Member

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    It's not that much, because in order to get the human mg/kg figure from the animal mg/kg figure, you have to first divide by a certain conversion factor (these conversion factors are given on page 7 of this document). In the case of rats, you have to first divide the rat mg/kg figure by the conversion factor of 6.2 to get the human mg/kg.

    So if the dose feed to rats is 2.5 mg/kg, the equivalent dose feed to humans would be 0.4 mg/kg. So for a 100 kg human, that is 0.4 mg of capsaicin.

    So if you say 1 kg of habanero chilis contains around 6 mg of capsaicin, you'd need to eat around 67 grams of this chili.
     
  12. Skippa

    Skippa Anti-BS

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    Meh, sounds like a mild curry from my local restaurant ;)

    On another note... DA FUQ!!! I'd like to get those researchers and shove a chillie up their butt and force them to run a marathon.
     
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  13. RogerBlack

    RogerBlack Senior Member

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    I corrected - it's more than that.
    Having said that - I wholly support this sort of study - if this was a valid model of CFS.
    I am unsure if I support it now, but only because it is a distraction and their mouse model seems likely inadequate.
    I see no mention if they support PEM.

    I have rats and mice here - at times I have had problems keeping them out of my food and killing them.

    Should lab animals be well treated as far as possible - yes.
    Should we value them over other animals of the same species in the wild - no.
     
  14. trishrhymes

    trishrhymes Senior Member

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    It might be interesting to do a study where rats are infected with a virus that makes them ill but that rats usually recover from.

    Then get one group to do forced exercise while still ill and another group to rest as much as they need to.

    Would some of the exercise group show signs of chronic fatigue a few weeks later, while the rested group recover?

    And could they then do a 2 day CPET (cardio-pulmonary exercise test) to see whether the fatigued rats had PEM.

    If so, then they might actually have a rat model of ME....
     
  15. RogerBlack

    RogerBlack Senior Member

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    I do wonder if the US/... army holds sufficient records and these could be accessed.
    Basic training has lots of extreme physical action that the soldier may not easily be able to avoid while they have a virus, or at the least they may be forced back in early.

    It seems this is damn near ideal for triggering CFS, if it is in fact virus + exertion.
    They may not have enough records, and may not take useful samples though.

    As to mice - that would be an interesting experiment - may need a _lot_ of mice, depending on the prevalance, and it might be very complex if it requires different strains of mice to pick up a sensitive strain.

    Possible viruses * strains of mice * prevalance = lots and lots of mice.
     
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  16. alex3619

    alex3619 Senior Member

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    I would like to see this tried.
     
  17. alex3619

    alex3619 Senior Member

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    I think some version of this might be doable.
     
  18. trishrhymes

    trishrhymes Senior Member

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    I suggested virus plus exercise because that's my experience of how my ME started - going back to work while still ill, pushing myself to keep going despite feeling really unwell - and never recovering.

    I also suggested it because I remember reading Melvin Ramsay's book about the Royal Free outbreak and the observation that lots of the patients and medical staff had the infection that was going round, but the patients who were in bed being looked after recovered, whereas lots of the staff who continued working got ME.
     
  19. Hip

    Hip Senior Member

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    I keep meaning to write to a few ME/CFS researchers to suggest this idea to them (the idea that administering corticosteroids to mice acutely infected with CVB might create a genuine mouse model of ME/CFS).
     
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  20. Theodore

    Theodore Senior Member

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