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Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study, 2021, Bourke, White et al

Discussion in 'Psychosomatic research - ME/CFS and Long Covid' started by Andy, Oct 3, 2021.

  1. Andy

    Andy Committee Member

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    Highlights

    • Central sensitisation (CS) was assessed using quantitative sensory tests (QST).
    • Dynamic QST showed complete agreement in all subjects regarding the presence of CS.
    • The large majority of CFS and fibromyalgia cases demonstrated CS.
    • This could be either a cause or an effect of these conditions.


    Abstract

    Introduction

    Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation.

    Methods
    19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM).

    Results
    CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146–311; p = 0.04) and FM cases (Median 189 kPa; IQR 129–272; p = 0.003) compared to HC (Median 311 kPa; IQR 245–377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3–27.7) vs HC = 14.2 °C (9.0–20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2–44.0) vs HC = 45.3 °C (40.1–46.8); p = 0.03) pain thresholds, where CFS cases did not.

    Conclusion
    Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders.

    Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0022399921002695
     
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  2. petrichor

    petrichor Senior Member (Voting Rights)

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    "endophenotype"
     
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  3. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    I always wonder if there are participation biases involved in tests like this - given the thresholds are still subjectively reported, participants with the illness may believe they are supposed to be ultra-sensitive to such pain and thus report it sooner, even though it may be experienced similarly between ill participants and controls.

    There are a variety of biases that affect reproducibility. eg. https://pubmed.ncbi.nlm.nih.gov/29989267/
     
  4. Mithriel

    Mithriel Senior Member (Voting Rights)

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    I was trying to talk about central sensitization with my husband but realised I have no idea what they think it is beyond sensitizing centrally.

    It feels like a concept forced onto disease so top down rather than something pulled from careful study of patients so bottom up.

    It is a categorization which they are calling an endophenotype but they could do the same thing with eye colour.
     
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  5. rvallee

    rvallee Senior Member (Voting Rights)

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    "Central sensitization" will always be my favorite little thing in this ideology, it's literally "two turtles down" and not even subtle about it. Why are some people experiencing more pain? Obviously because they're more sensitive to it. And that World Turtle is obviously standing on top of that other World Turtle, how silly of you not to know that.

    I especially love that we are still living with the fiction that Peter D White has retired from research as an excuse not to provide the PACE data but also he's still out there copy-pasting stuff. I mean technically this doesn't count as research so it's mostly failing at candor but still. I guess this is just the control interval between bouts of pretending to "leave the field", which should be expected in a few months or so along with another whiny op-ed showing plainly how they don't give a single damn what happens to their patients.

    I also love how this crap gets published:
    Either or of two things, assuming the premise that those are the only two available options. Rain is either angels weeping or demons urinating, no other possible option because I say so. Then again, this is their own private journal so they can publish whatever they want, it's not as if there's a serious editing process behind this.
     
    Last edited: Oct 3, 2021
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  6. petrichor

    petrichor Senior Member (Voting Rights)

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    I think their use of the term endophenotype is ridiculous. They ran a study that pretty much found that patients with CFS and FM are more sensitive to pain, and then they're calling it an endophenotype, when that hasn't remotely been established as an endophenotype in any way, shape or form?

    This paper is just trying to take a really banal experiment and throwing in a bunch of buzzwords to make it sound like it's far more than it is. Which, I don't think is good science. And to me, it makes them look like they don't have any idea how science works.
     
  7. NelliePledge

    NelliePledge Moderator Staff Member

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    Again White spending time ‘retired from CFS research’ that could have been better spent sorting out release of the full anonymised PACE data.
     
  8. Milo

    Milo Senior Member (Voting Rights)

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    CSS is a construct and is not diagnosed via any objective testing.

    Quantitative sensory testing (QST) is a panel of diagnostic tests used to assess
    somatosensory function, in the context of research and as a supplemental tool in the diagnosis of somatosensory disorders, including pain insensitivity, painless and painful neuropathy. The panel of tests examine a broad range of different sensations, including hot, cold, touch, vibration. It has both positive and negative tests (can test for increased or reduced sensitivity). QST reflects a formalisation of existing neurological tests into a standardised battery designed to detect subtle changes in sensory function.[1] Large datasets representing normal responses to sensory tests have been established to quantitate deviation from the mean and allow comparison with normal patients. It is thought that a detailed evaluation of somatosensory function may be useful in identifying subtypes of pain and as a potential tool to identify a symptomatic neuropathy,[2] which may represent up to 50% of total people with neuropathy (or loss of the nerve fibres). In clinical use, it is often combined with other tests such as clinical electrophysiology.[3] In research settings it is increasingly applied in combination with advanced imaging such as fMRI, epidermis "nerve" biopsies and microneurography to classify subtypes of painful disorders.[4]


    https://en.wikipedia.org/wiki/Quantitative_sensory_testing
     
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  9. Hutan

    Hutan Moderator Staff Member

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    White, out of 'retirement' to poke people with FM and CFS until they say it hurts. Not surprised.

    I'm not even sure about this idea that people with ME/CFS have lower pain thresholds, let alone the CSS interpretation overlaid on that idea. From memory, the experimental results, even when done by researchers wanting the lower pain threshold idea to be true, have been inconsistent. Certainly I don't think I am unusually sensitive to pain.

    Seriously? Would someone really complain that something 22.6°C was causing pain due to it being cold? Or would something 38°C (which is, after all, similar to body temperature) cause someone to report pain due to it being hot? I'd be surprised if this was a reproducible result. If it's true, it certainly deserves a better response than a waving away with some vague theory.

    I haven't read the paper.
     
    Last edited: Oct 4, 2021
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  10. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    My n=1 response is that for me the opposite may be true. It is hard to be objective about subjective experience that can not be independently calibrated, but one of the idiopathic pains I experience is toothache. My subjective experience of idiopathic toothache is that it is as painful as such as an abscess or an impacted wisdom tooth, indeed it may only be retrospectively possible when examined by a dentist to differentiate between the pain with and the pain without identifiable associated dental issues. However since the onset of my ME, I believe I cope with such pain more easily and am likely to wait much longer before thinking about visiting a dentist. Further this was also the case when my ME was milder and visiting a dentist was much less of a challenge than now.

    However, this may not be the case with my sensory hypersensitivities when in PEM. The threshold for noise or bright light becoming painful is then much lower. Yet I would want to distinguish between the threshold for a specific sensory experience becoming painful and my threshold for tolerating pain, though perhaps the authors of this study might dismiss this as sophistry. The increased sensitivity tends to be modality specific, whereas I assume any theory of central sensitisation would require all the senses to be equally effected at the same time.

    Subjectively the issues arising from hypersensitivities are broader than just the pain component, as brain fog increases and the ability to do other actions becomes impaired and any length of exposure will trigger further PEM; yet when experiencing pain in isolation such as chostochondritis and migraines, I am able to remain surprisingly calm and relaxed even if the pain is so bad as to trigger vomiting or even passing out. Also the more abstract severe pain of chostochondritis or a migraine, though it might be associated with PEM, as long as I am able to lie motionless through it, does not seem of itself to trigger further PEM. I also suspect since developing ME I am more able to deal with the pain of migraine or chostochondritis than I would have been able to do pre onset, though my chostochondritis only began some fifteen years into my ME.

    In summary I believe my threshold for coping with pain itself is higher than pre ME, even though the ME has resulted in a lowering of the threshold for specific sensory inputs becoming painful when in PEM. Further exposure to problematic sensory inputs will trigger further PEM which pain by itself does not.

    [edited to add the final two paragraphs and corrected some typos]
     
    Last edited: Oct 4, 2021
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  11. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    I assume that any central sensitisation theory would imply all the senses would be effected equally. For me I am generally only aware of sensory hypersensitivities when in PEM and there seems to be a hierarchy of senses, for example for me noise is the first to become problematic where as it is very unusual for touch to become an issue. I would place the senses in the following order, with the lower ones only becoming an issues in more marked PEM or at the times when PEM has become constant:
    1. Sound
    2. Light
    3. Smell (& taste?)
    4. Temperature (more extreme than the range discussed in the paper under discussion)
    5. Touch
    As discussed in my previous comment, when in PEM sensory input can more readily become painful and distressing, but also this involves increasing brain fog and if sustained risks triggering further PEM. Interestingly pain itself, without sensory overload, be it idiopathic or linked to identifiable organic issues such as a tooth abscess or a migraine triggered by a specific food stuff, does not seem to increase brain fog or trigger further PEM.
     
  12. Trish

    Trish Moderator Staff Member

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    Moved post - accidentally posted on the wrong thread.

    It occurs to me that there is also an additive effect. If someone already has extensive pain, which everyone with FM and a lot of people with ME already have, and, for the research they have been told to stay off their pain meds in order to take part, any additional pain stimulus is coming on top of what is already being endured. So it's not so much that we are more sensitive to pain, but that we are getting more pain 'stimulus' from the additive effect than the person without constant pain will get.

    To make the experiment realistic, they should have found a way to mimic the 'background' FM pain level in the healthy subjects too, so the effect of the added test pain stimulus has the same additive effect.
     
    Last edited: Oct 4, 2021
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  13. Mithriel

    Mithriel Senior Member (Voting Rights)

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    That is it exactly, Peter. I have learnt to thole pain because I have no other choice. I had a root canal done without anaesthetic and when she touched the nerve it was painful but no worse than the nerve pain I often get when I am trying to sleep.

    But I can't bear noise or light. Certain noises incapacitate me so I can't think in the same way the myalgia of ME affects me.

    Basically, ME is a painful disease - the myalgia part is the clue - and part of the disease is also problems with sensory issues.

    They are like people who ask a couple of questions and then put their own interpretation on it from their ignorance instead of taking a careful history. From my own experience, doctors would ask something but their conclusions from my answer were not what I meant. They should be taught to follow up by saying what they think the answers mean.

    For instance I might say that I do not like going to parties because I feel bad for the next few days. I mean PEM they writ in my notes "heavy drinker often has long hangovers". If they said that I could explain I don't drink, it is the noise which makes me so ill.
     
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  14. spinoza577

    spinoza577 Senior Member (Voting Rights)

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    I would assume, in my opinion more precisely: ... would imply that all the senses would be potentially effected equally.

    In this manner a central sensitisation theory may well be able to explain the range of differences seen in PwME, which is sticking out enough even if it is difficult to deal with it in details (though I have the expectation that scientists are able to put things together).

    It also could lead to the question: which structure might be (directly or indirectly) effected so that different sensations (or even deeds) can be bulging high? I think, it could well be a structure responsible for distribution of inputs, or a structure for whole brain homeostasis. Sadly such scope is not seen in any science here.
     
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  15. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    That is not a reasonable assumption - most documented 'central sensitivity' phenomena are normal spinal responses to abnormal peripheral stimulation and occur even in healthy people. The irony is that most animal models require constant peripheral stimulation to induce the 'central sensitivity'.
     
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  16. Sean

    Sean Moderator Staff Member

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    That seems relevant.

    The placebo effect also does not persist. Coincidence?
     
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  17. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    Quote from the study:

    "Statement of funding
    The study was funded by project grants from Barts Charity (470/ 1700), the CFS Research Foundation and Action for ME."​
     
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  18. ME/CFS Skeptic

    ME/CFS Skeptic Senior Member (Voting Rights)

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    Yes, I wonder if people who are chronically ill might simply be more prone to report symptoms or findings (because they hope it will help their doctors or scientific research). Would be interesting to include a control group with an illness where pain is not a prominent symptom.
     
  19. Milo

    Milo Senior Member (Voting Rights)

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    Central sensitization is also inserting itself in Long-COVID. Scary times.
    OMG
     
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  20. petrichor

    petrichor Senior Member (Voting Rights)

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    I personally think it's very plausible people with ME are more sensitive to pain than healthy controls, although I wouldn't necessarily trust a study like this to establish that. However why that is, what that means, and whether it has any kind of significance are incredibly open questions.
     

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