Exercise is a tricky topic in fibromyalgia. Scan the titles of studies touting the positive effects of exercise in FM and you might be excused for entertaining visions of FM patients happily bicycling, running, doing jump jacks, and pumping weights.

woman-tired

People with fibromyalgia are not running marathons – or even running

That would be a mistake. Yes, exercise studies indicate that regular exercise is helpful but most exercise prescriptions for FM are so limited that, according to the American Heart Association, they still don’t provide enough exercise to protect FM patients from the adverse health consequences of having a sedentary lifestyle. Even after doing the prescribed exercises people with FM would still  be described as being sedentary.

That’s about as  good as it gets. Moderate to high-intensity exercise usually causes FM patients to suffer from pain and stiffness for days, and high attrition rates in exercise studies are common. A recent survey on Health Rising suggested that post-exertional malaise may be a bigger inhibiting factor than pain in FM. Whatever the exercise protocols touted for FM, PEM is indeed alive and well in the disorder. This study attempted to figure out why it was happening.

IL-6 – Key Anti-inflammatory Factor

Thus far, studies suggest that neuroendocrine and immune problems may be blunting FM patients’ ability to exercise. Several anti-inflammatory factors including ACTH, cortisol, IL-10, and IL-1RA are up-regulated during exercise. All these factors appear to be attributed to IL-6 secretion by the muscle cells. Increased IL-6 production also appears to be associated with a reduction in pro-inflammatory cytokines.

repairman

Prior studies suggested poor muscle repair was contributing to the PEM in FM

Growth hormone (GH) also plays a role in keeping inflammation under control during exercise. Growth hormone released during exercise regulates the synthesis of IGF-1, which in turn regulates the production of pro-inflammatory cytokines and helps repair muscle microtrauma. Two past studies have found reduced growth hormone production during exercise to exhaustion in FM.

Studies suggest reduced growth hormone production during exercise in FM may be allowing pro-inflammatory cytokines such as TNF-a and IL-1b to activate the pain receptors in the muscles.

These researchers proposed that an impaired muscle repair response and a blunted anti-inflammatory response was causing FM patients to suffer from both muscle damage and an overwrought pain response after exercise.

The Study

They took blood samples from 20 FM patients and 16 healthy controls, inserted a catheter in a vein, and then exercised them to exhaustion while drawing blood three times during exercise and then 60 minutes after the exercise. Two and four days after the exercise more blood was drawn, and their pain sensitivity was measured. Serum GH, ACTH, IL-1β, IL-6, IL-8, IL-10, IL-1RA, and TNF-a were measured.

Results

Anti-inflammatory Response During and Just After Exercise Takes a Hit

In contrast to the former studies, exercise was not associated with reduced growth hormone levels. Three important anti-inflammatory factors — IL-10, cortisol, and ACTH — however, were significantly reduced in the FM patients during exercise.

inflammation

Reduced anti-inflammatory cytokine production was present during exercise

Cortisol is a hormone that affects metabolism and reduces inflammation in the body. This study follows on the heels of several others finding that FM patients tend to under-produce cortisol in response to a variety of stressors including hypoglycemia, “static muscle work”,  and an exercise test,

Reduced awakening salivary cortisol is also present in chronic fatigue syndrome (ME/CFS). Cook recently finding  of altered gene expression levels in the cortisol receptor (NRC31) post-exercise in ME/CFS suggests  cortisol problems paly a role in the exercise issues in both FM and  ME/CFS.

Since IL-10 levels are believed to be triggered by IL-6 production by the muscle cells during exercise, IL-6 levels were expected to decline in the FM patients, but they didn’t. It’s possible that FM patients’ muscles are pumping out normal levels of IL-6, but the signal IL-6 is producing to create more anti-inflammatory products such as IL-10 is not getting through.

The reduced anti-inflammatory response during exercise could very well play a role in the pain FM patients experience during moderate to intense exercise. If anti-inflammatory cytokines  are not preventing pain receptors from being activated FM patients could experience increased pain during exercise.

The Post-exercise Period

What about in the post-exercise period? It’s in the hours and days following the exercise, after all, that the real hit in both FM and ME/CFS occurs. It’s the mysterious pattern of increased pain and fatigue following exercise that is so debilitating. Did the same pattern hold?

It didn’t. The study found no difference in the levels of anti-inflammatory markers in FM patients vs. the controls in the days following the exercise. The study also did not find that the pain or muscle stiffness or any of the symptoms the FM patients experienced after exercise were associated with decreased anti-inflammatory markers.

The Immune System and Fibromyalgia

The role the immune system plays in FM remains a tantalizing mystery. The pain, stiffness, and depression found are classic signs of immune activation and inflammation, but consistent results in immune studies are lacking. As in ME/CFS the immune system has proved a tough nut to crack.

cytokine studies review finding evidence for increased cytokines (Il-Ra, IL-6 and IL-8) was belied by a recent study finding reduced levels of different cytokines ( IL-4, IL-5, and IL-13). Another study suggested Il-6 production in response to a challenge was greatly reduced in FM.  A 2010 review reported:

“There is some support in the literature for relationships among FMS symptoms and cytokines; however, there are discrepant findings related to whether proinflammatory and anti-inflammatory cytokines are elevated or reduced in persons with FMS and whether their levels correlate with the core symptoms of this disorder.”

Short term Inflammation All That’s Needed?

It’s possible that inflammation doesn’t need to last long to produce its effects.  A response to “stress” that was similar to what showed  up in  this study, appeared in the Dubbo studies – albeit on a much longer time scale.  In those studies an increased degree of immune activation early in an infection increased a person’s risk for coming down with ME/CFS.

Short periods of exercise-induced inflammation could trigger microglial activation and/or an increased sensitization to inflammatory byproducts (aka Miller’s reduced dopamine hypothesis) in ME/CFS.  Exposure of the central nervous system to inflammatory agents in laboratory animals can result in prolonged microglial activation in the absence of any evidence of inflammation in the body.

Another Direction

Against-the-FlowInflammation is not the only potential source of exercise-induced pain. The Lights have found indications of immune dysfunction in their gene expression ME/CFS/FM exercise studies, but receptors associated with assessing muscle damage and sympathetic nervous system activation appear to be more important. Increased levels of lactate and pyruvate in FM patients’ muscles have been found in several studies.

A recent fibromyalgia mouse-model study suggests that long duration pain triggered by exercise is produced differently from the pain produced by inflammation. It suggests that ion channel dysfunction of the sensory nerves associated with the muscles could be causing that pain without the involvement of inflammation.

It’s possible as well that the reduced anti-inflammatory response during exercise – which has now been seen in several studies – contributes to the ion channel or other exercise associated  problems in FM and/or ME/CFS.  There are lots of  options.

A Growth Field

This study found that something did go wrong with the immune system during exercise, but how to translate that into the post-exertional relapses FM and ME/CFS patients experience after exercise is unclear.

This  research and others are opening the door to understanding what happens to people with ME/CFS and FM when they exercise. It will take time and much  more research to fully understand  what is happening, but the sheer range of  factors being looked at  – from cytokines to cortisol to muscle metabolite receptors to brain functioning to aerobic capacity to muscle oxygen consumption to pH levels to mitochondrial functioning (take a breath) and probably more is gratifying.

Andrew Lloyd  recently joked that exercise studies are great for researchers seeking to understand ME/CFS and  rough on the patients who  engage in them, but it’s very encouraging that researchers are now focusing so intently on what is the defining characteristic for ME/CFS.





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