Fibromyalgia pain: Scientists may have finally solved the mystery

Fibromyalgia has always confused doctors and patients alike. It causes pain that spreads across the body, fatigue that lingers, and sleep that never refreshes.

People often describe it as invisible pain – constant but hard to explain. For years, science had no clear answer for why it happens.

A major new study changes that story. Scientists from deCODE Genetics and many global research centers analyzed data from more than 2.5 million people. Their work identified 26 genetic regions linked to fibromyalgia.

The findings finally reveal a biological foundation for a condition often misunderstood or dismissed.

Biggest genetic study so far

The study gathered genetic information from 11 large biobanks, including UK Biobank, FinnGen, deCODE Iceland, and others.

Together, the datasets covered 54,629 fibromyalgia cases and over two million controls. Researchers ran genome-wide scans to find tiny DNA differences more common in people with fibromyalgia.

To make the data comparable, each dataset went through strict quality checks. Any variant that looked suspicious or poorly measured was removed.

After combining all of the data, the team performed a massive meta-analysis – one of the largest of its kind for a chronic pain disorder.

Discovery in the brain

Among the 26 variants, one stood out. It appeared inside the Huntingtin gene, the same gene that causes Huntington’s disease when heavily mutated.

The fibromyalgia variant doesn’t trigger that condition, but it sits in a region important for neural maintenance. People carrying this variant had roughly nine percent higher odds of developing fibromyalgia.

This finding shifts the focus from muscles to the brain. It hints that fibromyalgia’s roots lie within neural circuits that control pain sensitivity, not within inflamed tissue or joints.

How fibromyalgia affects the brain

When researchers looked closer, they found that most genetic activity connected to fibromyalgia happened in the brain.

Enrichment tests showed signals clustering in cortical and subcortical areas, including the caudate nucleus and frontal cortex. A chart from the study displayed these tissues lighting up while others stayed quiet.

This pattern supports what clinicians have suspected for years – that fibromyalgia stems from a hypersensitive nervous system.

The brain and spinal cord amplify ordinary sensations, turning mild pressure into persistent pain. Genes like CAMKV, DRD2, MDGA2, and CELF4 appear central to this process.

Shared fibromyalgia pathways

The researchers also explored how these genetic changes connect to other diseases. Fibromyalgia shares DNA links with chronic fatigue, irritable bowel syndrome, and post-traumatic stress disorder. The same genetic variations influence pain, mood, and sleep regulation.

The overlap extends even further. Some variants appear in conditions such as long COVID and myalgic encephalomyelitis (also known as chronic fatigue syndrome).

That overlap suggests one underlying biological network may shape many seemingly different illnesses – all tied to nervous system regulation.

What genes reveal about symptoms

The 26 identified genes explain why fibromyalgia symptoms stretch beyond pain. Several affect neurotransmitters and brain development.

Others control cellular metabolism and immune responses. Taken together, they describe a disorder driven by communication errors between nerve cells rather than by direct tissue damage.

The study’s authors noted that people with fibromyalgia often experience brain fog, anxiety, or sleep problems.

The genetic results help connect these symptoms. When pain signaling misfires in the brain, every related function – thought, mood, and rest – becomes harder to regulate.

Fibromyalgia and autoimmune diseases

Fibromyalgia often gets confused with autoimmune diseases like rheumatoid arthritis or lupus. Both cause chronic pain, but their roots differ.

This genetic study found no strong signals in the immune system’s major gene region, known as the MHC. That makes fibromyalgia unlikely to be a traditional autoimmune condition.

Still, mild connections appeared between fibromyalgia and immune-related traits such as white blood cell count. The evidence suggests some immune involvement but not enough to define the disease as autoimmune.

Instead, it points to an interaction between brain and immune pathways that affect how the body handles stress and inflammation.

The question of gender

Fibromyalgia affects women far more than men. Yet genetics tell a different story. The study found no difference in genetic architecture between sexes. Men and women shared almost identical risk profiles.

This means that environment, hormones, and life experiences probably amplify the shared genetic risk rather than create separate ones.

The imbalance seen in clinics may reflect those external factors rather than differences in DNA.

Potential tools for early detection

Researchers built polygenic risk scores – calculations that estimate someone’s genetic likelihood of developing fibromyalgia.

People with the highest scores were significantly more likely to have the condition. These scores are not yet precise enough for clinical use, but they could become powerful tools for early detection in the future.

Such approaches might help identify people prone to chronic pain before symptoms worsen, guiding early lifestyle or medical interventions.

Fibromyalgia pain and daily life

Beyond disease links, the study uncovered correlations with sleep patterns, metabolism, and body weight.

Genes associated with insomnia, obesity, and type 2 diabetes overlapped with fibromyalgia’s risk genes. That overlap explains why patients often report fatigue, sluggish metabolism, or difficulty maintaining energy.

The findings also reveal the true complexity of fibromyalgia pain. It doesn’t come from one gene or one trigger. Instead, many small genetic effects work together, shaping how the brain perceives and processes discomfort.

Clear therapeutic targets revealed

The newly discovered genetic map offers clear therapeutic targets. The Huntingtin regulator GPR52 already serves as a drug target in Huntington’s disease research.

Modifying its activity could help in fibromyalgia as well. Another gene, CELF4, under investigation for chronic pain therapy, now becomes relevant here too.

These connections create a hopeful path toward precision medicine. Future treatments may focus on restoring healthy nerve signaling rather than just dulling pain perception.

Many challenges remain

The study depends on medical records for diagnosis, which may misclassify some patients. Many cases go undiagnosed, while others receive fibromyalgia codes for overlapping conditions.

Most participants were of European ancestry, making it essential to include more diverse populations in upcoming research.

Despite these gaps, the dataset remains the most comprehensive ever assembled for fibromyalgia. It moves the conversation from uncertainty to measurable biology.

The authors of the paper are affiliated with institutions including the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Massachusetts General Hospital, the University of Helsinki, and the University of Copenhagen.

The study is published in the journal medRxiv.

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