The cause of<unk>  is unknown. However, several risk factors, genetic and environmental, have been identified. Genetics Genetics play a major role in<unk> , and may explain up to 50% of the disease susceptibility.<unk>  is potentially associated with polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems. Several genes have been suggested as candidates for susceptibility to<unk> . These include SLC64A4, TRPV2, MYT1L, NRXN3, and the 5-HT2A receptor 102T/C polymorphism. The heritability of<unk>  is estimated to be higher in patients younger than 50. Neuropathic pain and major depressive disorder often co-occur with<unk>  – the reason for this comorbidity appears to be due to shared genetic abnormalities, which leads to impairments in monoaminergic, glutamatergic, neurotrophic, opioid and proinflammatory cytokine signaling. In these vulnerable individuals, psychological stress or illness can cause abnormalities in inflammatory and stress pathways that regulate mood and pain. Eventually, a sensitization and kindling effect occurs in certain neurons leading to the establishment of<unk>  and sometimes a mood disorder. Nervous system Stress Woman feeling emotional stressStress may be an important precipitating factor in the development of<unk> . A 2021 meta-analysis found psychological trauma to be strongly associated with<unk> . People who suffered abuse in their lifetime were three times more likely to suffer from<unk> , people who suffered medical trauma or other stressors in their lifetime were about twice as likely. Some authors have proposed that, because exposure to stressful conditions can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis, the development of<unk>  may stem from stress-induced disruption of the HPA axis. Several studies have linked<unk>  with a previous "hyperactive" lifestyle, where a person goes beyond his or her limits and neglects basic bodily needs such as food and rest. This lifestyle has been hypothesized to increase the allostatic load and contribute to a state of physical deconditioning.<unk>  is frequently comorbid with stress-related disorders such as chronic fatigue syndrome, posttraumatic stress disorder, irritable bowel syndrome and depression. Personality Although some have suggested that<unk>  patients are more likely to have specific personality traits, when depression is statistically controlled for, it appears that their personality is no different than that of people in the general population. Lifestyle Poor lifestyles including being a smoker, obesity and inactivity may increase the risk of an individual developing<unk> . Sleep disturbances Impaired sleep is a risk factor for<unk> . In 1975, Moldofsky and colleagues reported the presence of anomalous alpha wave activity (typically associated with arousal states) measured by electroencephalogram (EEG) during non-rapid eye movement sleep of "fibrositis syndrome". By disrupting stage IV sleep consistently in young, healthy subjects, the researchers reproduced a significant increase in muscle tenderness similar to that experienced in "neurasthenic musculoskeletal pain syndrome" but which resolved when the subjects were able to resume their normal sleep patterns. Mork and Nielsen used prospective data and identified a dose-dependent association between sleep problems and risk of<unk> . Improving sleep quality can help<unk>  sufferers minimize pain. Non-celiac gluten sensitivity Non-celiac gluten sensitivity (NCGS) may be an underlying cause of<unk> -like symptoms but further research is needed. Other risk markers Other risk markers for<unk>  include premature birth, female sex, cognitive influences, primary pain disorders, multiregional pain, infectious illness, hypermobility of joints, iron deficiency and small-fiber polyneuropathy.
Fibromyalgia
Osteoarthritis
Polymyalgia rheumatica
Rheumatoid arthritis
Complex regional pain syndrome
Myofascial pain syndrome
Thyroid disease
Calpainopathy