Pathophysiology of Fibromyalgia
Fibromyalgia is fundamentally a disorder of central sensitization, where the central nervous system amplifies pain signals despite no evidence of actual tissue damage, nerve injury, or inflammation. 1
Core Mechanism: Central Sensitization
The primary pathophysiologic mechanism is central sensitization, in which the central nervous system develops heightened sensitivity to pain signals, leading to widespread pain without peripheral tissue damage or nerve injury 1
Fibromyalgia is classified as a "nociplastic" pain condition by the International Association for the Study of Pain, distinct from neuropathic or inflammatory pain, because pain arises from altered nociception despite no clear evidence of actual or threatened tissue damage 1
This represents a fundamental disorder of pain processing in the brain and spinal cord, not a peripheral problem—fibromyalgia is a central nervous system disorder, not a peripheral neuropathy 1
Alterations in Pain Processing
Ascending pain pathways are altered, with enhanced transmission of pain signals from the periphery to the brain, contributing to widespread hyperalgesia 2
Descending pain inhibition pathways are dysfunctional, with impaired endogenous pain modulation systems that normally suppress pain signals 3
These alterations in both ascending and descending central nervous system pathways, along with peripheral pathway changes, lead to heightened pain sensitivity characteristic of fibromyalgia 2
Contributing Factors
Genetic Influences
Familial aggregation of fibromyalgia has been demonstrated, with genetic research showing that fibromyalgia clusters in families along with related disorders such as major depressive disorder 3
Genetic factors contribute to susceptibility, though specific genes remain under investigation 4
Stress and Environmental Triggers
Physical and psychosocial stressors serve as environmental triggers that can precipitate or exacerbate fibromyalgia in genetically susceptible individuals 3, 5
Exposure to stressors contributes to dysfunctional pain processing through alterations in stress response systems 4
Neuroendocrine and Autonomic Dysfunction
Abnormal autonomic nervous system function contributes to altered pain perception and pain inhibition 3, 5
Neuroendocrine abnormalities in stress response systems may contribute to the pathophysiology, with aberrant responses potentially affecting pain processing 3
Clinical Manifestations of Central Sensitization
The pathophysiology manifests clinically as chronic widespread pain, fatigue, non-restorative sleep, mood disturbance, and cognitive impairment 1
Additional symptoms including Raynaud's phenomenon, irritable bowel syndrome, and temperature intolerance can be associated with this central sensitization process 6
Fibromyalgia frequently co-occurs with other conditions that may share common pathophysiologic mechanisms, including major depressive disorder, migraine, and irritable bowel syndrome—these may represent a group of "affective spectrum disorders" with shared heritable causal factors 5
Diagnostic Implications
Normal laboratory results and imaging support rather than exclude the diagnosis of fibromyalgia, as there is no organic tissue damage or inflammation 7
Fibromyalgia should be recognized as a positive clinical diagnosis based on characteristic features of central sensitization, not as a diagnosis of exclusion 1
The absence of peripheral pathology is expected and consistent with the central nervous system origin of symptoms 1
Common Pitfall to Avoid
- Do not attribute fibromyalgia symptoms to peripheral nerve damage or seek peripheral causes—this fundamentally misunderstands the pathophysiology as a central nervous system disorder of pain amplification 1