Pathophysiology of Fibromyalgia
Fibromyalgia is fundamentally a disorder of central pain processing characterized by central sensitization—an amplification of pain signals in the brain and spinal cord—rather than peripheral tissue damage or inflammation. 1, 2
Core Pathophysiological Mechanisms
Central Sensitization and Altered Pain Processing
The primary mechanism is central sensitization, where the central nervous system amplifies pain signals, leading to widespread pain despite no evidence of actual tissue damage or nerve injury. 1, 2, 3
Patients experience heightened pain sensitivity (hyperalgesia) and pain from normally non-painful stimuli (allodynia) due to alterations in both ascending and descending pain pathways in the central nervous system. 3, 4
There is dysfunction in endogenous pain inhibition systems—the brain's natural pain-dampening mechanisms fail to work properly, allowing pain signals to persist and amplify. 4, 2
Nociplastic Pain Classification
Fibromyalgia is classified as a "nociplastic" pain condition, distinct from neuropathic (nerve damage) or inflammatory pain, because pain arises from altered nociception despite no clear evidence of actual or threatened tissue damage. 1
This distinguishes fibromyalgia from conditions with identifiable peripheral pathology—laboratory tests and imaging are characteristically normal. 1, 5
Contributing Risk Factors and Triggers
Genetic and Familial Influences
Strong evidence demonstrates familial aggregation of fibromyalgia, suggesting heritable genetic factors contribute to susceptibility. 6, 4
Fibromyalgia may be part of an "affective spectrum disorder" group that shares common genetic vulnerabilities with major depressive disorder, migraine, and irritable bowel syndrome. 6
Stress and Environmental Triggers
Exposure to physical or psychosocial stressors can trigger or exacerbate fibromyalgia, with abnormal biological stress responses contributing to dysfunctional pain processing. 6, 4
Autonomic nervous system dysregulation and abnormal neuroendocrine responses (particularly involving the hypothalamic-pituitary-adrenal axis) play important roles in the pathophysiology. 6, 4
Neurotransmitter Abnormalities
Alterations in central monoaminergic signaling (serotonin, norepinephrine, dopamine) contribute to both pain amplification and associated symptoms like fatigue and mood disturbance. 2, 3
Imbalances in excitatory neurotransmitters (glutamate) and inhibitory neurotransmitters (GABA, glycine) further dysregulate pain processing. 2
Clinical Manifestations Beyond Pain
Multisystem Symptom Complex
While chronic widespread pain is the dominant symptom, fibromyalgia is heterogeneous and complex, with fatigue, non-restorative sleep, mood disturbance, and cognitive impairment ("fibro fog") commonly present but not universal. 1
These concomitant symptoms significantly impact quality of life and reflect the systemic nature of central nervous system dysfunction. 1, 2
Important Clinical Pitfalls
Do not mistake fibromyalgia for a diagnosis of exclusion—it is a positive clinical diagnosis based on characteristic features of central sensitization, not simply the absence of other findings. 7
Normal laboratory results and imaging support rather than exclude the diagnosis, as fibromyalgia involves no organic tissue damage or inflammation. 5
Avoid attributing symptoms to peripheral nerve damage or seeking neuropathic causes—fibromyalgia is fundamentally a central nervous system disorder, not a peripheral neuropathy. 1, 5