Courtney Craig

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ME/CFS and Fibromyalgia: Chronic Inflammatory Conditions

Mary Alvizures

Understanding Chronic Inflammation: The Silent Smolder

Inflammation is a natural process essential for healing and defending the body. In acute cases, it manifests as redness, heat, pain, and swelling. However, when inflammation becomes chronic, the symptoms are less overt, but cellular damage continues. Chronic inflammation often arises when the triggering agent, such as a virus or pollutant, isn’t eliminated, or when the immune system fails to suppress the inflammatory response.

The Role of Inflammation in Chronic Disease

While some degree of inflammation occurs naturally as part of aging, excessive inflammation contributes to numerous chronic conditions, including:

  • Diabetes.

  • Heart disease.

  • Cancer.

  • Autoimmunity.

  • Neurodegenerative diseases.

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are also increasingly recognized as chronic inflammatory conditions. Both are associated with heightened oxidative stress and immune dysregulation.

Oxidative Stress: Inflammation’s Partner in Crime

Chronic inflammation damages cells by:

  1. Producing excessive free radicals (reactive oxygen species).

  2. Depleting the body’s antioxidant defenses.

This imbalance perpetuates inflammation in a vicious cycle:

  • Free Radicals: Damage cell membranes, proteins, and DNA, triggering the release of inflammatory cytokines.

  • Cytokines: Increase oxidative stress, fueling more free radical production.

The result is widespread cellular dysfunction, a hallmark of both ME/CFS and fibromyalgia.

The Inflammatory Cascade: Key Players in Chronic Inflammation

All inflammatory processes function through cascades—a series of interconnected cellular events. Understanding the main players in these pathways provides insights into potential therapeutic targets.

1. Tumor Necrosis Factor-Alpha (TNF-α)

  • Produced by immune cells like macrophages, T cells, and microglia.

  • Regulates fever, viral replication, and cell death.

  • Overproduction is linked to conditions like depression, psoriasis, and rheumatoid arthritis.

2. Nuclear Factor Kappa-B (NFkB)

  • Activated by TNF-α and interacts with DNA to regulate immune responses.

  • Chronically active in diseases like inflammatory bowel disease, asthma, and heart disease.

3. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)

  • Activates the body’s antioxidant defenses and supports liver detoxification.

  • Helps recycle glutathione, the body’s master antioxidant.

  • Dysregulated in conditions like neurodegenerative diseases and chronic viral infections.

While over-the-counter anti-inflammatory drugs target downstream processes, more potent treatments like TNF inhibitors (e.g., Humira, Enbrel) act upstream but may suppress the immune system, leaving patients vulnerable to infection.

Inflammation in ME/CFS: Evidence and Implications

Immune Dysregulation

  • Studies show elevated levels of pro-inflammatory cytokines like IL-6 and TNF in ME/CFS patients.

  • ME/CFS patients often have a shift from Th1 to Th2 immunity, perpetuating inflammation.

Oxidative Stress

  • Increased free radicals, such as nitric oxide and peroxynitrite, have been directly measured in ME/CFS patients.

  • Deficiencies in antioxidants like CoQ10, zinc, and glutathione contribute to heightened oxidative stress.

Neuroinflammation

  • Activated glial cells produce pro-inflammatory cytokines in the brain, leading to neuroinflammation.

  • Neuroinflammation underpins symptoms like:

    • Brain fog.

    • Fatigue.

    • Exercise intolerance.

These processes may explain phenomena like post-exertional malaise and heightened pain sensitivity (allodynia and hyperalgesia). Research in ME/CFS has detected neuroinflammation and this may underpin the cardinal symptoms of the condition: brain fog, fatigue, exercise intolerance. Here are a few examples:

Nakatomi, Y et al. (2014) Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. J Nucl Med Vol. 55 no. 6 945-950

Shungu, DC, et al (2012) Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed. 25(9):1073-87.

VanElzakker MB et al (2019) Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Front Neurol. 9:1033.

Inflammation in Fibromyalgia: What Research Reveals

Cytokine Imbalances

  • Elevated levels of IL-8, IL-6, and IL-17 in fibromyalgia patients suggest an inflammatory burden.

  • Increased anti-inflammatory cytokine IL-10 may indicate the body’s attempt to compensate for inflammation.

Oxidative Stress in Fibromyalgia

  • Immune cells in fibromyalgia patients show reduced CoQ10 and elevated free radicals.

  • This imbalance reduces antioxidant defenses, exacerbating chronic inflammation.

Neuroinflammation has also been studied in fibromyalgia. Here are several examples:

Natelson BH et al. (2015) Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial. J Pain. 16(11):1211-9.

Bäckryd E et al. (2017) Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. J Pain Res. 10:515-525.

Natelson BH, et al. (2017) Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia. Fatigue. 5(1):15-20.

Moving Forward: Targeting Inflammation Safely

Addressing inflammation in ME/CFS and fibromyalgia requires therapies that:

  • Reduce oxidative stress.

  • Modulate inflammatory pathways without compromising the immune system.

While many pharmaceutical options target the inflammatory cascade, natural compounds may provide safer alternatives by modulating key inflammatory players like TNF-α, NFkB, and Nrf2. Here are some supplements that do just that.

Final Thoughts: ME/CFS and Fibromyalgia as Inflammatory Conditions

Both ME/CFS and fibromyalgia are characterized by chronic inflammation and oxidative stress. Understanding the inflammatory pathways involved can guide targeted treatments that alleviate symptoms without disrupting the immune system. By addressing the root causes of inflammation, patients may find relief from the debilitating symptoms of these conditions.

References

Maes, M & Twisk, F (2009) Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you: disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways may explain cardiovascular disorders in ME/CFS. Neuro Endocrinol Lett. 30(6):677-93.

Maes M, Mihaylova I, & Bosmans E. (2007) Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. Neuro Endocrinol Lett. 28(4):456-62.

Coskun Benlidayi, I. (2019). Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatology International.

Bocci, V & Valacchi, G. (2015) Nrf2 activation as target to implement therapeutic treatments. Front Chem. 3: 4.