Understanding Why Physical or Mental Exertion Causes Symptom Flares in ME/CFS and Fibromyalgia

Living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia can be incredibly challenging, especially when physical or mental exertion leads to a significant flare in symptoms. This phenomenon, known as post-exertional malaise (PEM) in ME/CFS, can leave sufferers feeling debilitated for days or even weeks. But why does this happen? Understanding the underlying mechanisms can help us manage these conditions more effectively.

Nervous System Response

Autonomic Nervous System Dysfunction

Both ME/CFS and fibromyalgia involve dysregulation of the autonomic nervous system, which controls involuntary bodily functions such as heart rate, digestion, and respiratory rate. When this system is dysfunctional, the body might react abnormally to stressors, leading to symptoms like fatigue, pain, and cognitive issues .

Central Sensitization

In fibromyalgia, central sensitization plays a significant role. This means the central nervous system (brain and spinal cord) becomes hypersensitive, amplifying pain signals. Normal activities that would not cause pain in healthy individuals can trigger significant pain responses in those with fibromyalgia .

Immune System and Inflammatory Response

Immune Dysregulation

There is evidence suggesting that immune system dysfunction, including chronic low-level inflammation, may be involved in both conditions. After physical or mental exertion, the immune system may overreact, leading to increased symptoms .

Neuroinflammation

In ME/CFS, there is growing evidence that neuroinflammation (inflammation in the brain) could contribute to symptoms. Physical or mental exertion might exacerbate this inflammation, leading to increased fatigue, pain, and cognitive dysfunction .

Cellular Energy Production

Mitochondrial Dysfunction

Mitochondria are the energy powerhouses of cells. In ME/CFS and fibromyalgia, there is some evidence suggesting that mitochondrial function may be impaired. This impairment means that cells do not produce energy efficiently, leading to rapid depletion of energy reserves with exertion and prolonged recovery times .

Delayed Onset Muscle Soreness (DOMS)

While there are some similarities to the concept of DOMS, where muscle soreness occurs after unfamiliar or strenuous exercise due to microscopic muscle damage and inflammation, the mechanisms in ME/CFS and fibromyalgia are more complex and systemic. In these conditions, the whole-body response to exertion is dysregulated, not just the muscles .

Brain Signalling

Pain and Fatigue Signalling

The brain's signalling pathways that modulate pain and fatigue may be altered in these conditions. After exertion, the brain might over-amplify pain and fatigue signals, leading to the characteristic symptoms of a flare .

How mental exertion can lead to physical symptoms in Fibromyalgia, ME/CFS & FND

Dysregulation of the Stress Response System

• HPA Axis Dysfunction:

• In ME/CFS, fibromyalgia, and FND, there is often dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.

• Chronic mental stress can lead to an abnormal cortisol response, affecting the body’s ability to handle stress and causing widespread physical symptoms, including muscle pain.

• Sympathetic Nervous System Hyperactivity:

• Persistent mental stress can lead to a state of sympathetic nervous system (SNS) hyperactivity.

• This results in prolonged muscle tension, reduced pain threshold, and increased perception of pain, contributing to muscle pain and stiffness.

Central Sensitization

• Increased Sensitivity to Pain:

• Central sensitization is a key feature in fibromyalgia and is also seen in ME/CFS and FND.

• It involves heightened sensitivity of the central nervous system (CNS) to pain signals, leading to amplified pain perception from stimuli that wouldn’t normally be painful.

• Neuroinflammation:

• Chronic mental stress can lead to neuroinflammation, which may exacerbate central sensitization.

• This inflammation can alter pain processing pathways in the brain, increasing muscle pain and stiffness.

Neurotransmitter Imbalance

• Altered Serotonin and Norepinephrine Levels:

• Mental exertion can affect the levels of neurotransmitters like serotonin and norepinephrine, which play a role in pain modulation.

• Imbalances in these neurotransmitters can lead to increased pain sensitivity and muscle stiffness.

• Endorphin Deficiency:

• Chronic mental stress can deplete endorphin levels, the body’s natural painkillers.

• This can lead to heightened pain perception and muscle discomfort.

Psychogenic Factors

• Somatic Symptom Amplification:

• Psychological stress can lead to increased focus on and amplification of physical symptoms.

• This can create a cycle where mental stress exacerbates physical symptoms, which in turn increases stress, perpetuating muscle pain and stiffness.

• Emotional Stress and Muscle Tension:

• Emotional stress often results in increased muscle tension, particularly in the shoulders, neck, and back.

• Prolonged mental exertion can lead to sustained muscle tension and eventual pain and stiffness.

Immune System Dysregulation

• Chronic Inflammation:

• Mental stress can trigger immune system dysregulation, leading to chronic low-grade inflammation.

• This inflammation can affect muscles and joints, contributing to pain and stiffness.

• Cytokine Imbalance:

• Stress-induced cytokine release can affect muscle and nerve function, contributing to the physical symptoms seen in these conditions.

Feedback Loops

• Mental-Physical Feedback Loop:

• Mental stress leads to physical symptoms, which then cause more mental stress, creating a vicious cycle.

• This loop can perpetuate and intensify muscle pain and stiffness.

• Reduced Physical Activity:

• Mental fatigue and stress can lead to reduced physical activity.

• Physical inactivity can result in muscle deconditioning and increased stiffness and pain when activity is resumed.

How minor physical exertion can lead to symptom in Fibromyalgia, ME/CFS & FND

Dysregulation of the Stress Response System

• HPA Axis Dysfunction:

• In these conditions, there is often dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.

• Minor physical exertion can cause an exaggerated or insufficient cortisol response, impairing the body’s ability to recover and leading to symptoms like fatigue and muscle pain.

• Sympathetic Nervous System Hyperactivity:

• Physical exertion, even minor, can exacerbate the hyperactivity of the sympathetic nervous system (SNS) in these conditions.

• This can lead to prolonged muscle tension and increased pain perception, resulting in muscle pain and stiffness.

Central Sensitization:

• Increased Sensitivity to Pain:

• Central sensitization is a hallmark of fibromyalgia and is also present in ME/CFS and FND.

• This condition leads to an increased sensitivity to pain, where even minor physical exertion can trigger significant pain and discomfort.

• Neuroinflammation:

• Physical activity can exacerbate neuroinflammation, which is common in these conditions.

• This inflammation can affect pain pathways in the brain, increasing pain and stiffness following minor exertion.

Neurotransmitter Imbalance:

• Altered Serotonin and Norepinephrine Levels:

• Minor physical exertion can further disrupt the levels of neurotransmitters like serotonin and norepinephrine, which are crucial for pain modulation.

• These imbalances can lead to increased pain sensitivity and muscle stiffness.

• Endorphin Deficiency:

• Physical activity typically increases endorphin levels, but in these conditions, endorphin production may be impaired.

• This can result in a lack of natural pain relief, making minor exertion more painful.

Psychogenic Factors:

• Somatic Symptom Amplification:

• The anticipation of pain from physical activity can lead to increased focus on and amplification of physical symptoms.

• This can create a feedback loop where minor physical exertion exacerbates symptoms, which then increases stress and further physical discomfort.

• Emotional Stress and Muscle Tension:

• Physical activity can increase emotional stress and muscle tension in individuals with these conditions.

• This leads to a cycle of increased pain and stiffness from even minor exertion.

Immune System Dysregulation

• Chronic Inflammation:

• Minor physical exertion can trigger or exacerbate immune system dysregulation, leading to chronic low-grade inflammation.

• This inflammation can affect muscles and joints, causing pain and stiffness.

• Cytokine Imbalance:

• Physical exertion can lead to an imbalance in cytokine production, which affects muscle and nerve function.

• This can result in increased pain and fatigue after minor physical activity.

Feedback Loops

• Physical-Mental Feedback Loop:

• Physical exertion leads to physical symptoms, which cause mental stress, creating a vicious cycle.

• This loop can perpetuate and intensify symptoms, making minor exertion significantly impactful.

• Reduced Physical Activity:

• Symptoms following minor exertion can lead to reduced physical activity.

• This inactivity can cause muscle deconditioning and increased stiffness and pain when activity is resumed.

Energy Production and Metabolism

• Mitochondrial Dysfunction:

• Mitochondrial dysfunction, often seen in ME/CFS and fibromyalgia, leads to inefficient energy production.

• Minor physical exertion can deplete limited energy reserves, resulting in severe fatigue and muscle pain.

• Oxidative Stress:

• Physical activity can increase oxidative stress, which is already elevated in these conditions.

• This can damage cells and tissues, contributing to pain and fatigue after minor exertion.

Conclusion

In ME/CFS, fibromyalgia, and FND, the body’s abnormal response to even minor physical and mental exertion involves a complex interaction of physiological, neurological, and psychological factors. The brain’s response to stress, involving dysregulated HPA axis activity, central sensitization, neurotransmitter imbalances, immune system dysregulation, and psychogenic factors, can all contribute to the manifestation of muscle pain and stiffness following mental or physical exertion, and is not solely due to muscle strain or typical soreness.

Understanding these mechanisms helps in developing better treatment strategies that address both mental and physical aspects of these conditions.

References

Clauw DJ. Fibromyalgia and related conditions. Mayo Clin Proc. 2015.

Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DEJ. Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM. 2007.

Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011.

Komaroff AL, Cho TA. Role of infection and neurologic dysfunction in chronic fatigue syndrome. Semin Neurol. 2011.

Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007.

Nakatomi Y, Mizuno K, Ishii A, et al. Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: an 11C-(R)-PK11195 PET study. J Nucl Med. 2014.

Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009.

Tomas C, Newton J, Watson S. A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. ISRN Neurosci. 2013.

Cheung K, Hume P, Maxwell L. Delayed onset muscle soreness: treatment strategies and performance factors. Sports Med. 2003.

Cook DB, O'Connor PJ, Lange G, Steffener J. Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. NeuroImage. 2007.