The Pain of Exercise

Chronic fatigue syndrome is not the only disorder featuring  post-exertional malaise.  Widespread pain may be fibromyalgia’s main symptom but exercise problems, while not  as severe as found in ME/CFS,  are common.

Exercise intolerance in FM and ME/CFS

People with chronic fatigue syndrome and fibromyalgia need to be careful about exercise. This study points a reason why

Most studies suggest that ‘exercise’  is generally  helpful for FM   but a CFS-like scenario still prevails; vigorous exercise such as running, biking, etc,  will throw an FM patient into bed and really vigorous exercise is almost unheard of.  Just as in chronic fatigue syndrome, most fibromyalgia exercise prescriptions focus on mild exercises such as walking, aquatic strengthening exercise, qigong, tai chi, etc.

Fibromyalgia is four times as numerous as ME/CFS, is associated  more with  pain – a much more  active field of study than fatigue – and  has three FDA approved drugs. Chronic fatigue syndrome is the exertion inhibited disorder par excellence – but FM with its painful muscles  has gotten more muscle studies.

Something strange is going on in fibromyalgia to cause the exercise intolerance there  and researchers are zeroing in on the same area in both FM and chronic fatigue syndrome – blood flows and the muscles.

The Study

In this study researchers used an hybrid near infrared spectroscopy (NIRS) technique to measure three important features of producing energy;  how much blood was flowing to the muscles, how much oxygen was present, and how much oxygen was actually taken up by the muscles.

Large blood flows flood the muscles (or should flood the muscles) during exercise to deliver oxygen for aerobic energy production and  wash away toxic byproducts ( such as  lactic acid).


This study found FM patients muscles  were getting the blood  they needed but for some reason they weren’t taking up the oxygen very  quickly and it took longer for the oxygen levels of their cells to get back  to normal after exercise.  At least two things could explain this strange finding.

Mitochondria Problems?

The mitochondria use  oxygen to produce energy;  since damaged mitochondria don’t use as much oxygen, damage to the mitochondria could explain the low oxygen uptake in FM.  Damaged mitochondria  also often pump out large numbers of cell damaging free radicals which could interfere with muscle metabolism and cause pain.

 Or A Debt Too High?

oxygen debt

An ‘oxygen debt’ caused by too much lactate or other substances could be interfering with oxygen uptake by the cells.

During exercise enormous amounts of oxygen are needed to neutralize the lactate and other toxic  by products created during exercise.  This is called ‘repaying the oxygen debt’;  it  took much longer for FM patients to repay that debt than expected.

The  normal  muscle blood flows suggested there was more than enough blood flow to ‘clean up’ the lactate the muscles produced. If the  muscles were producing more lactate and other toxic by-products than normal, however, then the oxygen present might be going to clean up that rather than getting used up by the mitochondria.

Reduced Blood and Oxygen Flows a Critical Element  in FM and Chronic Fatigue Syndrome?

More FM studies than not have found reduced blood flows to the muscle and several ME/CFS studies have as well.  These researchers didn’t find reduced blood flows but they did find reduced oxygen uptake which suggested the cells were in an ischemic state – and that could be the key to the whole shebang.

‘Ischemia’ occurs when  blood flows to a tissue are low enough to  reduce the levels of  oxygen and glucose needed for cellular energy production.  The problem is actually not the ischemia per se but what comes after it;  in what must be one of nature’s weirdest tricks, re-infusing tissues that have been deprived of oxygen  with oxygen again can cause  a serious problem called ‘reperfusion injury’.

free radicals

Reperfusion injury can cause high levels of membrane damaging free radicals

It turns out that the absence of oxygen – which means the switching on of anaerobic metabolism and the production of toxic-by products – creates an environment packed for inflammation.

Oxygen is a mild free radical and throwing it back into an oxygen deprived environment can result in an explosion of stronger free  radicals such a nitric oxide, superoxide and finally peroxynitrite  (eg. Dr. Pall’s).  Bizarrely, as that’s going on white blood cells may also bind to the endothelial cells lining the small blood capillaries, once again blocking the flow of the blood.

Hibernating animals get around reperfusion injury by limiting the activity of their anaerobic energy production pathways. That’s an interesting fact given that studies indicate that people with ME/CFS enter into anaerobic energy production very quickly while exercising. Simply walking can be sufficient to exhaust their capability to generate energy aerobically.  Some ME/CFS doctors use exercise tests to determine the heart rates at which people with ME/CFS enter into anaerobic energy production.  Could people with ME/CFS/FM be creating ischemic zones by regularly entering into anerobic energy production?

It’s very clear that the reperfusion injury in a significant event like a heart attack – where blood flows have been almost completely cut off – is very damaging but it’s not clear how much of a problem lesser amounts of ischemia are.

The Sympathetic Nervous System and Fibromyalgia… Again

Several researchers believe that ischemia induced pain plays a key role in the reduced activity and ‘deconditioning’ sometimes found in FM.  Elvin  concluded that muscle ischemia induced pain played a key role in FM patient’s activity limitations. He felt that the reduced muscle blood flows following exercise that he found in FM could be explained by deconditioning, sympathetic nervous system issues and/or ischemia induced pain.

Kulshreshtha proposed that an overactive sympathetic nervous system caused a vasoconstriction (narrowing) of the blood vessels. The narrowed blood vessels produced a low oxygen (hypoxic) state which caused pain.  The Light’s proposed that a similar vasoconstriction decreased blood flows to multiple parts of the body  causing  the buildup of metabolites and inflammatory agents. The Light’s finding of a huge buildup of muscle injury sensing receptors in ME/CFS/FM could conceivably be caused by need to constantly monitor the muscles for signs of reperfusion induced injury.

Another study found that increased vasodilation of the blood (increased parasympathetic nervous system functioning) is associated with decreased pain in FM pointed.

Martinez-Lavin’s finding that intramuscular norepinephrine injections (sympathetic nervous system activator) increased pain in most FM patients but not in healthy controls suggests FM is a ‘sympathetically maintained syndrome’.

Blood Vessel Issues

Reduced capillary density in FM could also limit blood flows.  The endothelial walls of the blood vessels appear to be thickened in FM and increased arterial stiffness has been found in ME/CFS.  Damaged blood vessel walls often result in more vasoconstriction. Interestingly, stress and chronic pain appear to be sufficient to negatively impact blood vessel walls.

Once this process gets started it tends to feed on itself;  hypoxia and pain  trigger more sympathetic nervous system activity possibly causing further constriction of the blood vessels and further reductions in blood flow.

Muscle-Brain Connection

Note that this process is could be happening across the body. Shungu found both decreased blood flows and increased lactate levels (300% higher!) in his ME/CFS patients brains.  Because lactate levels are a function of anaerobic metabolism the high lactate levels suggest that a hypoxic (low oxygen) state is present.

Could Poor Microcirculation Be Causing Chronic Fatigue Syndrome (ME/CFS)?

Natelson found similarly increased lactate levels in FM patients brains. When Savella works it appears to do so, at least in part, by reducing lactate levels. Vermoulen proposed that the increased brain and muscle lactate levels found in some ME/CFS studies probably derive from the same process.

Increased levels of pyruvate and lactate in the interstitial spaces of trapezius muscles pointed to an anaerobic state in fibromyalgia.  The same pattern, interestingly enough, was found in the trapezius muscles of people with trapezius myalgia but not in people with whiplash (and sore trapezius muscles) suggesting different metabolic problems exist in different pain conditions. The authors suggested increased pyruvate/lactate may be synonymous with central sensitization syndromes such as FM, CFS, IBS, etc.).

Cause of Upper Body Pain in Fibromyalgia (and ME/CFS?) Identified? Plus: ‘Trapezius Myalgia’ – Another Sister Disorder Identified?

Reduced small blood vessel development (capillarization), degraded type II muscle fibers and evidence of mitochondrial disturbances in Type I muscle fibers suggested significant muscle issues were present in FM.  Gerdle proposed that alterations in intramuscular ATP, phosphoreatinine  (PCr) and muscle fat content probably were probably caused by  activity limitations due to pain and problems with muscle mitochondria.

Note the theme here – researchers proposing that inactivity caused by muscle pain  in FM may result in deconditioning which exacerbates the initial problems.  Reduced capillary production, increased heart rate low blood volume, poor blood vessel functioning,  etc. can all be consequences of, or be worsened by, deconditioning.

Chronic Fatigue Syndrome (ME/CFS)

Significantly lowered blood volume is endemic in ME/CFS and blood volume enhancers such as salt, saline, NUUN and electrolyte enhancing drinks are commonly used.  A recent study suggested, fibromyalgia patients take note,  low blood volume – a very common problem in ME/CFS – is present in FM as well.

Blood vessel constriction

Are low blood flows producing oxygen depleted states in FM and chronic fatigue syndrome?

ME/CFS studies have suggested low blood flows (low oxygen states) are important. Vermeulen et. al concluded that the reduced aerobic metabolism  found in ME/CFS was probably due to low blood flows (read reduced oxygen flow) to the mitochondria.  Natelson concluded that the 20%  reduction in aerobic capacity  he found in people with ME/CFS was probably due to low blood flows caused by autonomic nervous system  dysfunction.

Some ME/CFS doctors agree. Dr. Bell’s book “Cellular Hypoxia and Neuro-immune Fatigue’  is focused entirely on the idea that hypoxic (low oxygen states) cause ME/CFS/FM.  Dr DeMeirleir believes the large blood vessels are overly opened  in ME/CFS while the small blood vessels are too tightly constricted to let enough blood to get to the tissues.  Dr. Cheney believes low blood flows are hampering gut and other functioning in ME/CFS.

Backwards System

Perhaps the oddest thing about the sympathetic nervous system activation in FM and ME/CFS is that it appears to be activated during rest and sleep and blunted during exercise. Essentially the fight/flight system is turned on during rest and then declines when presented with a challenge.  To put this into blood vessel terms; the SNS may be narrowing the blood vessels when you’re at rest but then failing to open them sufficiently when you’re active.

Treatment Connection

Phenylephrine’s ability to stop orthostatic intolerance in its tracks in a small ME/CFS cohort by increasing blood flows to the brain during a tilt test was remarkable. Dr. Julian Stewart suggested that some way has to be found to get more blood to the brain (and presumably the muscles) in these diseases.

Standing Clear: Drug Stops Orthostatic Intolerance in ME/CFS In Lab – Next Steps

The fact that several popular drugs used in ME/CFS/FM effect sympathetic nervous system functioning and the  blood vessels suggests they may be alleviating low oxygen states.

Kulshreshtha proposed  amytripyline’s efficacy in FM is due, at least in part, to its ability to open blood vessels and increasing blood flows to the muscles. The Lights found that low doses of propranolol, a sympathetic nervous system enhancing drug reduced pain, improved the ability to stand and moderately increased cortisol levels in FM patients. (They believe low dose propanolol reduces SNS activation by turning down overactive sensory receptors in the muscles. Normal dose propanolol, on the other hand, constricts the blood vessels causing more low oxygen states and pain).

Mestinon, a parasympathetic nervous system enhancing drug designed to tamp down sympathetic nervous system activation, has been very helpful for some.

Other drugs that can reduce SNS activity such as tricyclic antidepressants, duloxetine, pregbalin (lyrica),  venlafaxine and pindolol have been helpful in FM and other pain disorders.

A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise

Blood volume has been described as uniformly low in ME/CFS and may be low in fibromyalgia. Since low blood volume impedes blood flows to the tissues, blood volume enhancers may be able to help.

The Hummingbird and Avacen devices which attempt to increase blood flows to the body and brain might be helpful as well.

The Hummingbird: Could a Blood Flow Enhancer Help With Fibromyalgia, POTS and ME/CFS?

Exercise Implications

If low oxygen states are causing body-wide pain in ME/CFS and fibromyalgia then pushing patients with low aerobic capacity could be a recipe for more pain.   High amounts of aerobic exercise in FM typically result in more pain while lower levels of exercise can be helpful.  Some evidence suggests that short bouts of presumably non-aerobic resistance exercise can reduce pain and increase parasympathetic nervous functioning and heart rate variability.

Exercises that enhance oxygen delivery while putting little stress on the aerobic energy production system such as Tai Chia, yoga and qiGong are often recommended.


A recent FM study indicated problems with oxygen delivery to the tissues may be present. Significant evidence suggests that low oxygen states caused by low blood volume, overly constricted blood vessels and perhaps mitochondrial dysfunction  could be causing  pain and other problems in FM and ME/CFS.



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