HOW DID FIBROMYALGIA EVER BECOME A BRAIN DISEASE? DISENTANGLING CONJECTURE AND TRUTH

Introduction

In his seminal book Propaganda (1928) Edward Bernays [1891-1995] observed:

“The conscious intelligent manipulation of the organized opinions and habits of the masses is an important element in a democratic society. Those who manipulate this unseen mechanism of society constitute an invisible government which is the ruling power in our society.”

As this article will show, his words still ring true in the field of Rheumatology. That which commenced as conjecture on fibromyalgia has been repeatedly embellished to a stage where it has assumed the status of established knowledge or truth.

“Central sensitivity syndromes”

In 2007, Dr Muhammad Yunus from Illinois noted that a number of diverse medically controversial conditions, such as fibromyalgia, irritable bowel syndrome, tension-type headaches and chronic fatigue syndrome, had several clinical features in common. He attributed these features to “hyperexcitement of the central neurons”, which in turn led him to propose the “concept of central sensitivity syndromes (CSS)” [Yunus 2007].

A closer examination of this proposition reveals two assertions: firstly, central sensitisation (CS) of nociception was taken as the model from which a generalisation to “central sensitisation” was made; secondly it was stated that the biology of CSS is “based on neuroendocrine aberrations (including CS) that interact with psychosocial factors to cause a number of symptoms”. How these undefined biochemical aberrations within the body “interact” with such extra-corporeal “factors” was never clarified.

This concept of “central sensitivity syndromes” should be seen as a bold proposition that there may be a common pathogenesis for the symptom clusters (technically not syndromes) under consideration. Although at that time “evidence for CS is not present in all patients of the CSS family”, the proposition was plausible and indeed the author stated explicitly, “The concept of CSS seems viable”. This can be seen as an example of a conjecture being raised to the status of a truth simply because if it were true so much that is currently not understood may become so [Lipton, 2005]. But is it true?

“Centralized pain”

Rheumatologist Dr Dan Clauw and his colleagues at the University of Michigan not only championed the cause of CSS around the world, but also have gone much further than Yunus by introducing the concept of “centralized” pain. In their paper with a tantalizing title – “maybe it (pain) is all in their head” – Phillips and Clauw [2011] likened “augmented pain transmission” and “sensory amplification” to the volume control on a radio dial. They suggested that individuals might have different “volume control settings” on “their pain and central processing”. This is an attractive metaphor, perhaps, but one that suggests lack of understanding of contemporary concepts of nociception and pain.

They followed up this paper by defining their concept of “centralized” pain [Phillips & Clauw, 2013]:

For clarity, we will use terms such as central augmentation or amplification to refer more broadly to central mechanisms that enhance perception or modulation of pain differentially between individuals. We will use the term “centralization” of pain to refer to a common process that seems to occur to a vulnerable subset of individuals with any chronic pain state, wherein pain primarily due to peripheral nociceptive input is subsequently amplified by central factors, such that both peripheral and central factors are then contributing to the perception of pain by an individual.

In this assertion, note the language: “centralization of pain … seems to occur … with any chronic pain state…” and “… pain primarily due to peripheral nociceptive input is … amplified by central factors, such that both peripheral and central factors … [contribute] to … pain”? Did they not notice the tautology inherent in these statements? Is not the experience of pain itself the “perception”, not a thing that is “perceived”? And is not “perception” an emergent function of the brain? “Modulation” of nociception may be analogous to a volume control; “amplification” of the experience of pain is not quite so linear.

The paragraph quoted above could be restated simply as, “Any chronic pain state is a function of the brain and may be influenced by many factors”.

But just how is pain to be “centralized” – and who or what does the “centralizing”? Apparently “centralized” pain can be identified “when multifocal pain occurs in conjunction with other centrally mediated symptoms, such as fatigue, insomnia, memory difficulties, and mood disturbances.” Such individuals are then said to “have centralized their pain” [Phillips and Clauw, 2013].

This implies that polysymptomatic distress in association with (multifocal) pain defines that pain as “centralized”. This diagnostic methodology could be termed “guilt by association”, which is a recognised logical fallacy.

Clauw [2014] then proclaimed: 

“Fibromyalgia can be thought of as a centralized pain state. Centralized pain is a lifelong disorder beginning in adolescence or young adulthood manifested by pain experienced in different body regions at different times. “Centralized” refers to central nervous system origins of or amplification of pain. This term does not imply that peripheral nociceptive input (i.e. damage or inflammation of body regions) is not contributing to these individuals’ pain but rather that they feel more pain than would normally be expected based on the degree of nociceptive input.”

How is it known that this is a “lifelong disorder”? How can it be determined that any one feels “more pain than normally would be expected …”? How would an observer be able to determine this [Cronje & Williamson 2006]?

A “white paper” [Arnold et al. 2016] then appeared in which fibromyalgia was said to exemplify “centralized” pain and to result from “persistent neuronal dysfunction” (See their Fig 1). Here is their argument:

“Aberrant neurochemical processing of sensory signals in the CNS may lower the threshold of pain, amplify normal sensory signals, and alter gene expression, thereby leading to hypersensitivity and central sensitization that result in chronic pain” [Arnold et al. 2016].

In this context, what is the “threshold of pain”? And how might “alter[ed] gene expression” lead to “hypersensitivity”. Of what and to what do “hypersensitivity and central sensitization” refer?

Returning to his dial-on-the-radio metaphor, Clauw [2015] asserted, “the pathophysiological hallmark is a sensitized or hyperactive central nervous system that leads to an increased volume control or gain on pain and sensory processing.”

Translated, that statement can be written as, “Increased CNS activity leads to increased pain and sensory processing”, which is a circular and tautological conjecture.

FM as a brain disorder/disease

According to Sluka and Clauw [2016], the overlapping conditions drawn together as CSS by Yunus [2007] are in fact manifestations of an underlying brain disorder with “similar underlying pathology with alterations in central nervous system function leading to augmented nociceptive processing and the development of central nervous system (CNS)-mediated somatic symptoms of fatigue, sleep, memory and mood difficulties.”

Translated, that statement can be written as, “Central sensitisation syndromes are characterised by the development of CNS-mediated symptoms attributable to altered brain function”. Or, to put it another way, a cluster of “CNS-mediated symptoms” allows the inference of a brain disorder called “central sensitisation”. This is yet another circular and self-fulfilling argument.

Further research

In 2017 the National Institute of Health awarded Michigan Medical School researchers, Drs Chad Brummett and Dan Clauw, funding of US $7.5 million to expand their work on the metaphor of the radio dial.

As Dr Clauw explained:

“For those with fibromyalgia, it’s like the brain turns up the volume control on pain processing. The high volume is often the underlying problem, more than damage or inflammation in the region of the body that hurts.”

In terms of contemporary neuroscientific knowledge of brain function, this comment makes no sense. Our brains are much more complex than are radio transmitters or receivers.

Conclusion

There may be validity in the proposition that the phenomenon of central sensitisation of nociception could be relevant to the pain experienced by patients who have been labeled with “fibromyalgia”. That is a theory from which testable hypotheses might be generated. Such an approach stands in marked contrast to statements such as “the brain turns up the volume of pain processing”, as if pain is a “thing” that can be “processed” including being “centralized”, or that “neuroendocrine aberrations interact with psychosocial factors” without outlining the biochemical basis of psychosocial factors, or that “chronic pain [is] caused by alterations in sensory processing in the CNS” which is equivalent to saying that the central nervous system is integral to the experience of chronic pain.

These and other statements should be seen for what they are: conjectures that appear plausible until it is recognised that their content is not amenable to hypothesis testing and thus are incapable of leading to the truth.

‘But the facts don’t exactly matter: people repeat them so often that you believe them. Welcome to the “illusory truth effect,” which is a glitch in the human psyche that equates repetition with truth [Dreyfuss 2017]’.

Such an effect is all too evident in this discourse where the main agenda is to promote fibromyalgia as a brain disease.

John Quintner & Milton Cohen

References:

Arnold LM, Choy E, Clauw DJ, et al. Fibromyalgia and chronic pain syndromes: a white paper detailing current challenges in the field. Clin J Pain 2016; 32(9): 737-746.

Clauw DJ. Fibromyalgia: a clinical review. JAMA 2014; 311(15): 1547-1555. Clauw DJ. Fibromyalgia and related disorders. Mayo Clin Proc 2015; 90(5): 680-692.

Cronje RJ, Williamson OD. Is pain ever “normal”? Clin J Pain 2006; 22: 692–699

Dreyfuss E. “Want to make a lie seem true? Say it again. And again. And again.” WIRED 11 February 2017. Link: https://www.wired.com/2017/02/dont-believe-lies-just-people-repeat/

Lipton P. The Medawar Lecture 2004: The truth about science. Philos Trans R Soc Lond B Biol Sci 2005; 360: 1259–69.

Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states – maybe it is all in their head. Best Pract Res Clin Rheumatol 2011; 25(2): 141-154.

Phillips K, Clauw DJ. Central pain mechanisms in rheumatic diseases: future directions. Arthritis Rheum 2013; 65(2): 291-302.

Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience 2016; 338: 114-129.

Yunus M. Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum 2007; 36(6):339-356.

9 Comments

  1. I appreciate the analysis. It does appear that the above researchers seem to oversimplify the condition of which there are many variables, not least of which is an adaptive nervous system.

    What do you think is leading to these symptoms in patients with fibromyalgia?

      • Thank you for that clear and succinct hypothesis. This suits my confirmation bias as I was already leaning towards that explanation.

        As a physical therapist, I see my role as helping the person suffering from chronic pain improve their robustness mentally and physically via simple, sustainable, and progressive exercise (usually strength training).

        I have so many questions as I think I may have your ear for the moment, but I’ll leave with one:

        In terms of your hypothesis, do you see the medical community at large moving towards your hypothesis or does it appear to be continuing down the same path that has lead us to things like dry needling (admittedly one of my biggest gripes of the PT profession)?

        • I wish I could answer your question in the affirmative. But, alas, the rheumatological community does not seem to have been receptive to at least considering our hypothesis.

          But I am reassured by the favourable responses received from people experiencing chronic widespread pain (aka fibromyalgia). They actually “get it”. I hope that this will be your experience, as well.

          Please continue to ask questions and I will endeavour to answer them.

          • I guess I already knew that would be the answer. The medical community seems to stumble from one favored treatment to the next.

            I do also find when explaining to patients about fibromyalgia with the stress response hypothesis that they will often get it as well.

            Thank you for your work.

  2. Applause for your analysis.

    When “fibromyalgia” is presented as a hypothesis to be studied (rather than an unchallenged axiom) the situation can get very clear.

    A simple enough way to dissolve the “brain disease” research conclusions is to realize the near-universal design flaw of using normal controls. If the fibromyalgia-labeled cases are compared to positive controls (e.g. pain from known sources), no doubt the claimed uniqueness of of the “pain-processing” findings would disappear.

  3. This article appeared last year in “RELIEF: PAIN RESEARCH NEWS, INSIGHTS AND IDEAS” brought to you by the IASP (International Association for the Study of Pain) Research Forum: http://relief.news/pain-101-looking-to-the-brain-to-understand-fibromyalgia-and-other-chronic-pain-conditions/

    It reinforces our opinion that the current discourse on fibromyalgia is dominated by those whose various conjectures are highlighted in the above article.

    By the way, does anyone else find the concept of “FM-ness” to be ridiculous?

  4. The various conjectures identified above are perpetuated in ongoing research being undertaken by Dr Clauw and his associates. They can be found in this abstract of a research project being undertaken by Drs Clauw and Brummett – Centralized Pain Phenotype as a Predictor of Opioid Non-Responsiveness. http://grantome.com/grant/NIH/R01-DA038261-02

    “Moderate to severe pain following surgery is common, even after surgeries thought of as minor. Opioids are the mainstay for acute postoperative pain care despite their known side effects and related adverse events. Most research to date has focused on the anesthetic and surgical factors associated with higher acute pain, thereby largely ignoring the inter-patient variability in pain sensitivity. As such, pharmacological adjuncts to opioids and regional anesthetics have been broadly applied in an all or none fashion rather than personalized based on patient characteristics. There is a growing appreciation of the importance of altered central nervous system (CNS) processing of pain and other symptoms in chronic pain states. The widespread body pain, hyperalgesia and comorbid symptomatology of centralized pain states has been best studied in fibromyalgia. Rather than being present or absent, fibromyalgia symptoms occur on a continuum that has been termed fibromyalgianess and can serve as a crude surrogate of the degree of centralization. Opioids are thought to be less effective in centralized pain patients. Our primary hypothesis is that although peripheral nociceptive input is important in the acute pain response, some patients possess varying degrees of CNS amplification (higher fibromyalgianess) that plays an equally or even more prominent role in the expression of pain and opioid consumption. Thus, we hypothesize that the patients with pain that is more centralized in that the degree of pain centralization as measured on a simple self-report measure strongly predicts acute opioid pain responsiveness by providing a surrogate measure of endogenous opioid tone. To test our hypothesis, we will conduct a prospective assessment of pain, opioid consumption and adverse acute postoperative period in patients undergoing total knee arthroplasty (n=200). These data will be used to assess whether fibromyalgianess predicts higher acute pain, more opioid consumption, and a lesser response of pain for the opioids administered. To assess the mechanistic underpinnings of these clinical findings, we will conduct preoperative functional imaging (fMRI and PET scanning) in 60 of the 200 knee arthroplasty patients across the continuum of fibromyalgianess to determine preoperative opioid tone and previously described brain imaging findings of hyperalgesia. The opioid consumption and pain reports will then be analyzed with the brain imaging findings. Consistent with our long term goal of personalized pain medicine, the proposed research could have a major impact on clinical practice because a subset of individuals could be easily identified who would be strong candidates for non- or reduced opioid acute analgesic regimens.

    Public Health Relevance

    A portion of all patients undergoing surgery experience moderate to severe pain and some patients seem to be less responsive to opioid pain medications. We suspect that some of this poor responsiveness can be predicted based on completing a brief questionnaire that measures the core symptoms of fibromyalgia. At the completion of this study we expect to have a better understanding of how characteristics of conditions such as fibromyalgia affect patients’ responses to pain after surgery and response to opioid (narcotic) pain medications. The information learned from this study would help to personalize pain care to the individual patient rather than simply treating people based on the surgery they are having.”

    I would like to draw attention of readers to this key sentence in the abstract: “Rather than being present or absent, fibromyalgia symptoms occur on a continuum that has been termed fibromyalgianess and can serve as a crude surrogate of the degree of centralization.” It is not made clear how the nebulous concept of “fibromyalgianess” can be used as a “crude surrogate” (marker?) for “the degree of “centralization”?

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