Fibromyalgia is not explained by a single gene or trigger. Instead, it represents a complex biological interaction between the body’s genetic blueprint and the environment that surrounds it.
Modern molecular research shows that genes can predispose individuals to greater pain sensitivity, but environmental influences such as stress, trauma, infection, and lifestyle often determine whether these genes are activated or remain silent.
This intricate connection between genes and the environment forms the foundation of what scientists call gene - environment interactions a central concept in understanding fibromyalgia biology.
The Genetic Susceptibility
Genetic studies have identified polymorphisms (small variations in DNA sequences) in genes related to neurotransmission, stress regulation, and immune response that may increase susceptibility to fibromyalgia. Read more
Among these, variations in:
SLC6A4 (serotonin transporter) , influences serotonin reuptake and mood regulation.
COMT (catechol-O-methyltransferase) , affects pain perception and dopamine metabolism.
MAO-A (monoamine oxidase A) , modulates stress-related neurotransmitters.
HLA (human leukocyte antigen) , linked to immune system sensitivity.
These genes do not directly cause fibromyalgia, but they may create a biological vulnerability where the body’s pain and stress responses become more reactive under certain environmental pressures.
Environmental Triggers and Lifestyle Influences
Environmental factors can act as epigenetic signals, modifying gene expression without altering the underlying DNA.
Commonly reported environmental contributors include:
Chronic psychological stress and emotional trauma
Sleep deprivation and irregular circadian rhythms
Viral or bacterial infections that activate immune pathways
Exposure to physical trauma or repetitive strain
Nutritional imbalance and oxidative stress
These factors can alter hormonal balance, neurotransmitter levels, and mitochondrial energy metabolism, potentially influencing how pain and fatigue are regulated in the central nervous system.
The Mechanism of Interaction: From Epigenetics to Gene Expression
The bridge between genes and the environment lies in epigenetic regulation processes that determine how genes are switched “on” or “off.”
Research has found that long-term exposure to environmental stressors can modify:
DNA methylation patterns in stress-response genes (such as NR3C1 and FKBP5).
Histone acetylation affecting chromatin structure and transcriptional activity.
Non-coding RNA (miRNA) expression, which fine-tunes gene activity at the post-transcriptional level.
These epigenetic changes can alter cellular signaling in neurons, glial cells, and immune cells, leading to the persistent hypersensitivity observed in fibromyalgia.
Neuroendocrine and Immune Pathway Involvement
The hypothalamic pituitary adrenal (HPA) axis is a major biological system connecting environmental stress to gene activity.
When stress becomes chronic, it can cause long-term changes in cortisol secretion, leading to altered neuroendocrine signaling and immune dysregulation.
At the same time, environmental factors such as infections or oxidative stress can activate cytokine networks (IL-6, TNF-α, IL-8), which interact with neuronal circuits that process pain.
This creates a feedback loop between the immune system and the central nervous system one that may be genetically predisposed in fibromyalgia patients.
Integrating Genetics and Environment in Fibromyalgia Research
Modern fibromyalgia research uses advanced tools such as:
Genome-Wide Association Studies (GWAS) to identify risk alleles.
Epigenome profiling to map methylation and histone patterns.
Transcriptomics (RNA-Seq) to study stress-induced gene expression.
Systems biology modeling to integrate multi-omics datasets.
These studies highlight that fibromyalgia is not caused by a single factor but by a dynamic network of genetic predispositions influenced by the environment an adaptive biological system that can shift under long-term stress exposure.
Conclusion
The biology of fibromyalgia can be best understood as a dialogue between genes and the environment.
Genetic predisposition sets the stage, but environmental influences from psychological stress to molecular oxidative signals decide how the script unfolds.
Through epigenetic regulation, these two forces continuously interact, shaping how cells respond to pain, fatigue, and stress.
Understanding this interaction at the molecular level offers promising insights into the complex systems biology underlying fibromyalgia and other chronic pain syndromes.