Fibromyalgia is a complex and poorly understood condition characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, cognitive issues ("fibro fog"), and other symptoms. Its exact cause remains unknown, but recent research has advanced our understanding. As of 2025, here are the most recent and emerging insights into possible causes and contributing factors of fibromyalgia:
1. Central Nervous System Dysregulation
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Central sensitization: A key theory is that the central nervous system (CNS) becomes hypersensitive, amplifying pain signals. This may involve altered neurotransmitter levels (e.g., increased substance P, decreased serotonin and norepinephrine).
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Brain imaging studies show abnormal pain processing and connectivity in regions related to pain and emotion.
2. Small Fiber Neuropathy
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Recent studies have found that many people with fibromyalgia have damage to small nerve fibers, which could explain pain and sensory abnormalities.
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This provides potential overlap with other neuropathic conditions and may offer new diagnostic avenues.
3. Mitochondrial Dysfunction and Oxidative Stress
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Evidence suggests impaired energy metabolism and increased oxidative stress in fibromyalgia patients.
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This might contribute to fatigue and muscle pain.
4. Immune System and Inflammation
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Low-grade systemic inflammation and altered cytokine profiles have been observed.
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Some research suggests fibromyalgia may involve neuroinflammation, especially in the brain and spinal cord.
5. Gut Microbiome Imbalance
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Newer studies indicate significant differences in the gut microbiota of people with fibromyalgia.
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This supports a gut-brain axis connection, potentially affecting inflammation, pain perception, and mood.
6. Infections and Viral Triggers
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Post-infectious fibromyalgia is increasingly recognized, particularly following infections like:
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Epstein-Barr virus
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Lyme disease
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COVID-19 (some long COVID symptoms closely resemble fibromyalgia)
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7. Trauma and Stress
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Physical or emotional trauma, including adverse childhood experiences, is a known risk factor.
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Chronic stress affects the hypothalamic-pituitary-adrenal (HPA) axis, which regulates pain and stress responses.
8. Genetic and Epigenetic Factors
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Genetic predisposition plays a role, especially in serotoninergic and catecholaminergic systems.
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Emerging research is exploring how epigenetic modifications (e.g., DNA methylation) may influence symptom development.
Takeaway:
Fibromyalgia is likely a multifactorial syndrome involving a combination of:
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Neurological dysregulation
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Immune and metabolic dysfunction
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Environmental triggers
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Genetic susceptibility
Ongoing research continues to explore biomarkers for diagnosis and more effective treatments. Find out more about these biomarkers here.
Related articles you may be interested in:
Findings Link Gut Bacteria and Fibromyalgia
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