The ME/CFS Zoo Hypothesis

A constant question regarding ME/CFS (and fibromyalgia) goes something like this:

Is it one disease, or is it a "spectrum", or is it multiple (distinct) diseases that look the same?

I that regard: I find the "Blind men and an elephant" parable helpful – and would like to expand it.

First of all, let me recount from the Wikipedia page a slightly modified summary of the parable:

In various versions of the tale, a group of blind men touch an elephant to learn what it is like. Each blind men feels a different part, but only one part, such as the trunk, or an foot, or the tusk.

A Jain version of the story says that six blind men were asked to determine what an elephant looked like by feeling different parts of the elephant's body. The blind man who feels a leg says the elephant is like a pillar; the one who feels the tail says the elephant is like a rope; the one who feels the trunk says the elephant is like a tree branch; the one who feels the ear says the elephant is like a hand fan; the one who feels the belly says the elephant is like a wall; and the one who feels the tusk says the elephant is like a solid pipe.

Afterwards the blind men talk to each other and learn that they are in complete disagreement. Some of the stories differ in how violent the conflict becomes, and how (or if) the conflict among the men and their perspectives is resolved.

In some versions, they stop talking, start listening and collaborate to "see" the full elephant. When a sighted man walks by and sees the entire elephant all at once, they also learn they are blind. While one's subjective experience is true, it may not be the totality of truth.

My impression is that many in the ME/CFS "community" think that most of the studies are equally "true" – I think that is the first mistake. To stay in the parable: Some of the blind men have never touched an elephant (or any other animal, for that matter) and simply make things up. Here you have blind men who describe not an elephant, but maybe an park bench, or an found umbrella, or maybe an object that exists only in their fantasy (and even describing that they suck). Yes Virginia, I'm talking about Lombardi, Mikovits and Ruscetti. There are others. Like those blind men trying to describe the color of the elephant. Somehow, now I have to think of the names Meirleir, Maes and Gerwyn.

And even if you sieve out all the blind men describing inanimate objects (or worse, make-believe objects), you get some who grabbed some random animal in the zoo and tried to described it. Now if they can describe two (or more) of those animals, and the differences between them, and if they do not try to make you believe that they describe the whole animal, I think they are much more trustworthy than those who want to make you believe they describe only an elephant, and that they know the entire elephant.

If you have someone who says "Here I found two animals with distinctly different tusk, one has leather like skin, the others is furry", well then we are on to something. Currently I have seen few people who would fit that bill: Alan Light (et al.), and maybe Julia Newton (come to my mind).

But one thing should be clear, all those harping about how we need better criteria to "sieve out all non-elephants" (to stay within the parable) should know that:
a) Your are an "blind men" yourself
b) You might be an "non-elephant" yourself
c) The studies you trust might describe non-elephants
d) The studies you trust might describe non-elephant animals that are different from you

Yes, better (and more stringent) criteria might be helpful, but what we need are ways to look at "a collection of zoo animals" (parable again), and learn to differentiate them properly, both in a research setting, and in a clinical setting.

Anecdote: Paleo helps for Fibromyalgia

Robb Wolf has the details.

Low-dose naltrexone: Better than nothing?

Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.
Younger J, Noor N, McCue R, Mackey S.

Stanford University School of Medicine, Palo Alto, California.

Abstract

OBJECTIVE:
To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo.

In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain.

Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.

METHODS:
Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study.

During the active drug phase, participants received 4.5 mg of oral naltrexone daily.

An intensive longitudinal design was used to measure daily levels of pain.

RESULTS:
When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016).

Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep.

Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05).

Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.

CONCLUSION:
The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain.

The medication is widely available, inexpensive, safe, and well-tolerated.

Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication.

Color me unconvinced.

The results may be "significant" in the statistical sense – and then even barely, just look at the p-values and the small sample size. To me however they don't look significant in the common sense of the word.

LDN may help some patients, a bit – so I won't blame you if you do give it a try. A cure or significant help, LDN is not.

If the (small) benefits of LDN outweigh the side-effects, that can this study not answer.

Is Myalgic Encephalomyelitis (ME) an Neurological Disease?

First of all, let me say that Myalgic Encephalomyelitis (ME) is classified as a Neurological Disease (ICD 10 G93.3, or F286).

And I don't want to change that.

At least not now. Not until we know whether ME is one disease, or several distinct diseases, and until we know what the pathological processes at the root of ME are.

So regardless how ME is classified, what is the reality of ME? About that I want to speculate a bit.

Personally, I think it will turn out that the ME patient population, very much like CFS, will be composed of several diseases. Maybe there are, compared to CFS, less people who are (mis-)diagnosed with ME but have actually something else – but I doubt that ME is only one disease.

From the Norwegian Rituxan study by Fluge and Melle we know that a sizable portion of ME/CFS patients may have an autoimmune condition – which may or may not exclude neurologic problems to be the root cause. We can't tell from the Norwegian study one way or the other.

From the studies by Christopher Snell we know that VO2 max and exercise tolerance are reduced in a CFS patient population, which would point to cardiovascular causes, lung causes, or muscle-metabolic causes – a neurological root cause seems IMHO unlikely in the sub-group characterized by Dr. Snell, but still possible. The results from Dr. Snell are not particular specific and can be caused by different pathological processes, so there could be several diseases out there having the same VO2 max presentation (as seems already to be the case with other known non-CFS diseases).

From the studies by Kathleen and Alan Light we know that there are at least two sub-groups in the ME/CFS (and FM) patient population:

• People with a specific presentation of POTS like gene-expression
• People with a nonspecific presentation of fatigue and pain gene-expression

The specific POTS presentation may be indicative of a cardiovascular orgin, possibly with the involvement of endocrine system (beta-receptors seem to be implicated in a sub-group in the Lights studies). So the POTS sub-group IMHO may be one distinct disease, and I think it is unlikely to be several diseases.

The later sub-group (fatigue/pain) may IMHO most likely originate from metabolic problems in the muscle. It could be possibly caused by several pathways, which would possibly mean several distinct diseases.

These problems could in turn affect the brain in a negative way, showing up as neurological symptoms ("brain fatigue" or "brain fog", etc.)

So in conclusion, at the moment a sizable portion of patients seem to have a non-neurological root cause, especially hinted by the work of Kathleen and Alan Light.

Still, a minority of ME/CFS patients may be suffering from one (or more) – as of now – unknown and/or poorly understood neurological diseases – though it seems unlikely to me that a majority of ME/CFS patients have a neurological problem as root cause.

Of course, this does not preclude an neurological involvement in ME/CFS patients with non-neurological root causes.

This picture may change when more research brings us more data, until then we have to consider non-neurolgical etiologies for a majority of ME/CFS patients – I would not cling on to the neurological label forever.

Some Speculation on Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME)

There was recently a paper by an Israeli group about the question whether Fibromyalgia (FM) and ME/CFS are same. This was followed by some speculation in the ME/CFS community. The general assumption seems to be that some consider FM a distinct illness/disease, and ME an different distinct illness/disease, and that CFS is some sort of "catch all" category.

I recently speculated how the "landscape" for ME/CFS might look like. I came to the conclusion that once proper biomedical tests (like done in the currently running Lipkin study) yield results, that ME/CFS will be shown to consist of several discrete illnesses/diseases.

I think a similar picture will emerge for FM.

Furthermore I think some (but not all) of the illnesses/diseases that will be found to cause FM will be the same as will be found to cause ME/CFS.

And on a related note: Some people want to get rid of the "CFS" label – to which I say bravo! Alas, I have the impression these advocates consider ME one distinct illness/disease (which I think is wrong), and they think that CFS is some sort of hodgepodge. Well assuming it so, then there are still many people (and I mean many people) who have an diagnosis of CFS, but actually have this "distinct ME" illness/disease. By cutting off these ME patients, that have been misdiagnosed as CFS patients, what do you accomplish?

Furthermore, these advocates seem to have no problem that people with the diagnosis "CFS" get slandered as psycho(somatic) cases, as long as "their ME" illness/disease is taken seriously. To which I say: If you don't fight for protection of CFS patients from psychobabblers, then why should ME patients be protected from psychobabblers?

The Mayo Clinic scores high on the QDC

The Mayo Clinic tests "Amygdala Retraining Program" by Ashok Gupta (What's next? Thymus Retraining? Bone Marrow Retraining? Liver Retraining?) – time to put my QDC to use!

The study abstract says that "Of the 44 patients randomly assigned who completed baseline assessments, 21 patients completed the study (14 in the standard care group and 7 in the study group)."

This means that over half of the study participants dropped out of the study and only 7 people who were in the 'treatment' group completed the study. This means that the majority of the participants who were in the 'treatment' group didn't even think the study was worth finishing. I'm so sick of these crappy psychobabble studies not counting drop outs in their results, what a crock!

Posted by: beanier
Apr 19, 2012
http://www.prohealth.com/library/showarticle.cfm?LIBID=16932

Oh my, the QDC says the quack is strong in the Mayo Clinic and Ashok Gupta.

Give a man a reputation as an early riser, and that man can sleep till noon.
-- Mark Twain

I think the reputation of the Mayo Clinic as an early riser is not exactly founded in reality.

"40% of CFS patients seen by the Newcastle Service could in fact be diagnosed with other conditions"

Breakthrough magazine Autumn 2011

The correct diagnosis
Are we getting better at diagnosing ME/CFS?

At present, there are many ways of diagnosing ME, CFS, CFIDS, CFS/ME and ME/CFS – and just listing these acronyms illustrates the confusion that besets the field. Yet each new definition delivers only a “diagnosis of exclusion” of other conditions, based on clusters of vaguely defined symptoms shared with other illnesses. How valid a diagnosis of ME/CFS really is depends critically on the rigour of the initial clinical assessment, and the efforts expended to exclude other treatable conditions that might be causing the collection of symptoms.

The clinical guideline produced by the UK’s National Institute for Health and Clinical Excellence (NICE) in 2007 came up with its own variant of diagnostic criteria for “CFS/ ME” – new, unexplained, persistent/recurrent fatigue with a post-exercise component plus one or more of a range of common symptoms such as difficulty with sleeping, muscle and/or joint pain and headaches. …

The most important finding was that 103 (40%) of patients seen by the Newcastle Service could in fact be diagnosed with other conditions. As the Figure opposite shows, the most common alternative diagnosis in these patients was fatigue associated with a chronic disease (47% of all alternative diagnoses …). The next common alternative diagnosis was primary sleep disorder (20%), including 8 patients with obstructive sleep apnoea and 12 with another primary sleep disorder – an important finding since sleep disorders form a significant and potentially treatable diagnostic group. Furthermore, 15% of all alternative diagnoses were psychological/psychiatric illnesses (most commonly, depression, anxiety and post-traumatic stress disorder); 13% were “unexplained” but not ME/CFS (5.2% of total referrals); and 4% were cardiovascular disorders (vasovagal syncope in patients with fatigue symptoms, who also had a history of episodes of loss of consciousness, with the diagnosis made after a reproduction of symptoms in head-up tilt testing). [Other conditions included metabolic syndrome and coeliac disease.]

Prof. Newton’s results concur with those from two smaller service audits (Dundee 1993; Newcastle 2007), and reiterate that a significant minority of UK patients referred from primary care with a diagnosis of ME/ CFS can receive alternative, exclusionary diagnoses if investigated at a specialist clinic. And they illustrate that in the absence of a full clinical assessment (which most patients in the community have either never undergone, or last had many years ago), the diagnosis of ME/CFS can easily become a stopping-off point for clinically complex patients with a variety of different illnesses.

This problem is encountered not only in the UK. A fascinating commentary in 2008 in Minnesota Medicine (available online) described the difficulties experienced at a clinic in the USA for patients with fatigue, exercise intolerance and weakness (i.e., patients very like ME/CFS patients in the UK). After reporting on three paediatric cases (all of whom received serious, new diagnoses), the authors commented that, “a thoughtful and thorough physical exam can sometimes reveal otherwise hidden diagnoses”. Commentaries like this, and investigations like this one at Newcastle, certainly raise the question of which treatable diagnoses might be uncovered if all patients currently parked in the ME/CFS diagnostic layby were examined intensively at a specialist Centre of Excellence by thoughtful and thorough physicians.

The ideal would be for ME/CFS or the subtypes within to be diagnosed objectively with criteria based on clinical or laboratory measurements. …

Amen to the last.

The Null Hypothesis for ME/CFS

Wikipedia on the null hypothesis:

The typical null hypothesis at the outset of the experiment is that no difference exists between the control group and experimental group (for the variable being compared).

So on that basis, I would formulate the following null hypothesis for ME/CFS:

There exists no relevant difference between patients with ME/CFS and a healthy control group.

I'll just point to the work of Kathleen and Alan Light showed repeatedly that we can reject this null hypothesis. There exists a relevant difference between patients and a healthy control group – CFS patients are not healthy.

So we need a new null hypothesis:

There exists no relevant difference between patients with ME/CFS and patients with similar medical conditions.

So the first two medical problems that came to mind for Kathleen and Alan Light were deconditioning and multiple sclerosis. Again, they rejected this new null hypothesis – CFS patients are distinguishable from deconditioned persons and they can be distinguished from multiple sclerosis patients.

Another condition that is similar is Fibromyalgia. Now, it got interesting. With their biomarker, they found a significant overlapp between ME/CFS and Fibromyalgia. Many (but not all) patients with CFS have Fibromyalgia as well. Many (but not all) patients with Fibromyalgia have CFS as well.

It comes down to that "The Lights" say that they have a biomarker, that they can distinguish CFS patients both from healthy controls, and from some similar medical conditions, but barely from Fibromyalgia patients. (It is not a perfect biomarker, but it looks promising)

So we can not fully reject the last null hypothesis. What would a new null hypothesis on this basis look like?

ME/CFS and Fibromyalgia are overlapping illnesses from the same spectrum, but distinct from other illnesses.

I guess we need more research.

Adverse Events Attributable to Nocebo in Randomized Controlled Drug Trials in Fibromyalgia Syndrome

Clin J Pain. 2012 Feb 14. [Epub ahead of print]
Adverse Events Attributable to Nocebo
in Randomized Controlled Drug Trials
in Fibromyalgia Syndrome
and Painful Diabetic Peripheral Neuropathy:
Systematic Review.

Häuser W, Bartram C, Bartram-Wunn E, Tölle T.

Department of Internal Medicine I, Klinikum Saarbrücken, Saarbrücken
Department of Psychosomatic Medicine and Psychotherapy
Department of Neurology, Technische Universität München, München, Germany.

Abstract

OBJECTIVE:
The objectives of the study were to determine the impact of nocebo effects on adverse events (AEs) in drug trials in fibromyalgia syndrome (FMS) and painful diabetic peripheral neuropathy (DPN).

METHODS:
MEDLINE, CENTRAL, SCOPUS, and the databases of the U.S. National Institutes of Health and the Pharmaceutical Research and Manufacturers of America were searched until December 31, 2010.

Randomized controlled trials with a parallel design of any drug therapy compared with pharmacological placebo in patients with FMS and DPN were included.

Pooled estimates of nocebo effects (number of patients with at least 1 AE and dropping out due AEs) were calculated for placebo and true drug groups by a random effects model.

RESULTS:
Fifty-eight FMS (62 DPN) trials included a total of 5065 (5095) patients in placebo groups.

The quality of reporting the assessment strategy of AEs was poor in most trials. The pooled estimate of the event rate drop out rate due to AEs in placebo groups was

• 9.6 [95% confidence control (CI): 8.6-10.7] in placebo and 
• 16.3 (95% CI: 14.1-31.2) in true drug groups of FMS trials and was 
• 5.8 (95% CI: 5.1-6.6) in placebo and 
• 13.2 (95% CI: 10.7-16.2) in true drug groups of DPN trials.

Nocebo effects accounted for 72.0% (44.9) of the drop outs in true drug groups in FMS (DPN).

DISCUSSION:
Nocebo effects substantially accounted for AEs in drug trials of FMS and DPN.

Standards to assess and report AEs should be defined by regulatory agencies. Strategies to minimize nocebo effects in both clinical trials and clinical practice should be developed.

(via Co-Cure)

"The Concept of Incomplete Fibromyalgia Syndrome"

The Concept of Incomplete Fibromyalgia Syndrome:
Comparison of Incomplete Fibromyalgia Syndrome With Fibromyalgia Syndrome
by 1990 ACR Classification Criteria
and Its Implications for Newer Criteria and Clinical Practice.

Yunus MB, Aldag JC.
From the Department of Medicine, University of Illinois College of
Medicine at Peoria, Peoria, IL.

J Clin Rheumatol. 2012 Feb 12. [Epub ahead of print]

Abstract

BACKGROUND:
The 1990 American College of Rheumatology (ACR) classification criteria for fibromyalgia syndrome (FMS) has 2 components:

(a) widespread pain (WSP)
and
(b) presence of 11 or more tender points (TP) among possible 18 sites.

Some clinic patients fulfill 1 component but not the other.

We have considered these patients to have incomplete FMS (IFMS).

The purpose of this study was to examine the clinical and psychological differences between IFMS and FMS (by 1990 ACR criteria) because such comparison may be helpful to diagnose patients in the clinic.

METHODS:
Six hundred consecutive patients referred to our rheumatology clinic with our diagnosis of FMS were examined by a standard protocol to determine whether they fulfilled the 1990 criteria for FMS.

Both IFMS and FMS groups were compared in demographic, clinical, and psychological variables using appropriate statistical methods.

RESULTS:
One hundred twelve (18.7%) patients did not satisfy the 1990 ACR criteria and were classified as IFMS.

Symptoms in IFMS and FMS were similar, generally with less frequent and less severe symptoms in the IFMS group.

In IFMS, no significant difference was found among the WSP and TP component subgroups.

Both TP and WSP were correlated with important features of FMS.

CONCLUSIONS:
Fulfillment of the ACR 1990 criteria is not necessary for a diagnosis of FMS in the clinic.

For diagnosis and management of FMS in the clinical setting, IFMS patients, along with consideration of the total clinical picture, may be considered to have FMS, albeit generally mild.

(via Co-Cure)

"Pain Negatively Affects Cognition in Fibromyalgia"

Pain Negatively Affects Cognition in Fibromyalgia

February 6, 2012 (Miami Beach, Florida) — Pain is the primary factor contributing to cognitive impairment in patients with fibromyalgia syndrome, over and above depression, anxiety, fatigue, sleep complaints, and medication use, reported Stefan Duschek, PhD, from the University of Munich, in Germany, here at the 6th World Congress of the World Institute of Pain.

Patients with fibromyalgia scored worse than healthy control subjects on mathematical thinking and attentional control. "A large part of the variance on these tests was explained by pain," said Dr. Duschek in an interview with Medscape Medical News. "The most important factor underlying these deficits is pain, nothing else; it's not depression, it's not anxiety, but pain."
…

I'd be surprised if it is significantly different in ME/CFS.

Of interest, patients taking opiate medication performed better than those who were not (P < .05). "Our hypothesis was the opposite — that opiates disrupt cognitive function — but it makes sense; it reduces pain intensity so people can concentrate better," said Dr. Duschek.

(via)

Mortality in Fibromyalgia

Mortality in fibromyalgia

Abstract
Objective
To determine if mortality is increased among patients diagnosed as having fibromyalgia.

Methods
We studied 8,186 fibromyalgia patients seen between 1974 and 2009 in 3 settings: all fibromyalgia patients in a clinical practice, patients participating in the US National Data Bank for Rheumatic Diseases (NDB), and patients invited to participate in the NDB who refused participation. Internal controls included 10,087 patients with osteoarthritis. Deaths were determined by multiple source communication, and all patients were also screened in the US National Death Index (NDI). We calculated standardized mortality ratios (SMRs) based on age- and sex-stratified US population data, after adjustment for NDI nonresponse.

Results
There were 539 deaths, and the overall SMR was 0.90 (95% confidence interval [95% CI] 0.61–1.26). Among 1,665 clinic patients, the SMR was 0.92 (95% CI 0.81–1.05). Sensitivity analyses varying the rate of NDI nonidentification did not alter the nonassociation. Adjusted for age and sex, the hazard ratio for fibromyalgia compared with osteoarthritis was 1.05 (95% CI 0.94–1.17). The standardized mortality odds ratio (OR) compared with the US general population was increased for suicide (OR 3.31, 95% CI 2.15–5.11) and for accidental deaths (OR 1.45, 95% CI 1.02– 2.06), but not for malignancy.

Conclusion
Mortality does not appear to be increased in patients diagnosed with fibromyalgia, but the risk of death from suicide and accidents was increased.

Alan Light 2011 Lecture: Gene Expression Biomarkers for Chronic Fatigue & Fibromyalgia Syndromes

As a follow-up to the last post, here is his 2011 lecture (about 1 hour) by Alan Light for OFFER Utah about his very excellent ME/CFS gene-expression study.

This is objective data that there is biological reason for the symptoms [in ME/CFS and Fibromyalgia].

You may want to switch to 1080p HD to best view the slides.
(Part 1 Part 2 Part 3 Part 4 Part 5)

My take-home messages:

1. 70% of ME/CFS patients have Fibromyalgia (FMS) symptoms. And Fibromyalgia gets worse after exercise, even if the definition for FMS does not specify for it. And a majority of FMS patients (but not all) have ME/CFS symptoms.

2. TRPV1 contributes to the body's temperature set point.

3. Alan Light found a sensory definition of fatigue (The nerves at the muscle tell the brain "You are tired") in ME/CFS that contributes to the desire to use the muscles less. It is related to "actual" muscle fatigue ("The muscle is about to fail"), but it is not the same.

4. In both ME/CFS and FMS there is a 40% subgroup, that has a Ad2A (vasoconstriction) decrease. That gene is responsible for preventing orthostatic intolerance (OI / POTS). 70% patients with this gene expression profile have orthostatic intolerance, and 20% without have POTS (it might depend when and how you measure POTS).

5. FMS without CFS patients look like controls after execercise, but have different baseline levels. P2X4, TRPV1 and IL10 are expressed higher at baseline.

6. Gene expression as biomarker for ME/CFS and Fibromyalgia? Specificity 94% (6% of false negatives) and sensitivity of 65% (35% of false positives), good but not excellent biomarker, could be improved. Might be clinically available within 2 to 3 years.

7. The orthostatic subgroup should be treated differently.

8. Pregabalin or Gabapentin decrease the level of pain and of mental fatigue - maybe.

9. The cause could be increase of sensitivity of fatigue and pain, or dysfunction of the sympathetic nervous system.
(My comment, this the only flaw of Alan Light's work I can think of. He is leaving out one possibility: Of course it could be that there is an actual increase of fatigue and pain due to a pathologically increased muscle exhaustion in ME/CFS and FMS patients. If the nerves are sensing something, it could actually be there – doh!)

10. This is objective data that there is biological reason for the symptoms.
(Translated to English: "The psychosomatic school can go and f*ck themselves.")

As an addendum:
Don't miss Christopher Snell's 2012 lecture, which ties in nicely!

Alan Light 2007 Lecture: The Physiology of Chronic Pain and Fatigue

OFFER Utah (warning, their website plays music...) has a lot of lectures regarding ME/CFS on their OFFER Utah Youtube Channel. They have some very good and interesting lectures (and some less so). If you haven't already, you should subscribe to their Youtube channel, add the feed to your RSS-Reader, etc. ...

One very interesting video is this 44 minutes lecture by Alan Light:

"The Physiology of Chronic Pain and Fatigue" Dr. Alan R. Light.

This presentation by Alan R Light was made during the 2007 OFFER Provider's Conference. This lecture shows basically where Alan Light came from and his studies that lead up to the ME/CFS post-exertional gene-expression study "the Lights" (he and his wife Kathleen Light) have done together with Lucinda Bateman.

I had these take home messages:

1. Acute pain and fatigue sensing are protective and evolutionary important to prevent depletion or injury of important systems. If an living being has an impairment in sensing of pain and fatigue, it will usually die quite quickly. So there are multiple pathways in a living being to measure this information.

2. There are many concepts of fatigue. For ME/CFS fatigue is not sleepiness, fatigue is not failure of the muscle, but a sensory event – one could move the muscle with enough willpower.

3. The sensing of muscle-pain and fatigue happens by nerve sensory-endings located between the muscle and the blood vessels. Several metabolites (Lactate, ATP, pH/protons) are measured together by receptors (e.g. P2X4, P2X5, ASIC3, TRPV1) working together.

4. Fatigue and pain share receptors, but are not the same.

5. The sympathetic nervous system can restrict blood vessels to muscles that are not fatigued and increase blood flow to muscles that are.

6. Mononuclear blood cells have these receptors too, as they need to go "where the action is", where damage is, where things are going wrong and they are circulating through the muscles that are used.

7. Enhanced muscle pain is caused by cytokines, and if the blood flow is not increased (if the sympathetic nervous system does not regulate it properly), the metabolites in the muscles build up, and with it fatigue and pain.

8. The NIH (and the medical profession at general) are not interested and it is very difficult to get funding for these studies. All his research depends on the support by the university of Utah. There is some old medical "knowlegde" ("these receptors don't function at physiological ranges" etc.) that needs to be challenged and updated. This research that should have been done 25 years ago and the NIH is dragging its feet.
(I find it ironic that it is Alan Light's research in ME/CFS that improves the understanding in biological and medical sciences of how pain and fatigue work – after all the damage that Strauss et. al. have done with their psychosomatic bullshit, after all the damage Wessely and Sharpe are still doing today)

Don't miss Alan Light's 2011 follow-up lecture!

And don't miss Christopher Snell's 2012 lecture, which ties in nicely!

I have ME/CFS

I have ME/CFS, and/or possibly Fibromyalgia*, so the updates here will be erratic – you have been warned.

* I would dearly love to have a proper test to find out what I have (or haven't). Even better would be if the etiology of ME, CFS and Fibromyalgia were known – or the etiologies of all sub-groups, if there are differences.