fibromyalgia fibromyalgia fibromyalgia (fm) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. other symptoms include insomnia and a general hypersensitivity. not to be confused with myalgic encephalomyelitis (chronic fatigue syndrome) nor with myelofibrosis. fibromyalgiaother namesfibromyalgia syndrome (fms)the location of the 19 pain areas for the widespread pain index of fibromyalgiapronunciation/ˌfaɪbroʊmaɪˈældʒə/ specialtyrheumatology, neurologysymptomswidespread pain, feeling tired, sleep problemsusual onsetmiddle agedurationlong termcausesunknowndiagnostic methodbased on symptoms after ruling out other potential causesdifferential diagnosisanemia, autoimmune disorders (such as ankylosing spondylitis, polymyalgia rheumatica, rheumatoid arthritis, scleroderma, or multiple sclerosis), lyme disease, osteoarthritis, thyroid diseasetreatmentsufficient sleep and exercisemedicationduloxetine, milnacipran, pregabalin, gabapentinprognosisnormal life expectancyfrequency2% the cause of fibromyalgia is unknown, but is believed to involve a combination of genetic and environmental factors. environmental factors may include psychological stress, trauma, and certain infections. the pain appears to result from processes in the central nervous system and the condition is referred to as a "central sensitization syndrome". the treatment of fibromyalgia is symptomatic and multidisciplinary. the european alliance of associations for rheumatology strongly recommends aerobic and strengthening exercise. weak recommendations are given to mindfulness, psychotherapy, acupuncture, hydrotherapy, and meditative exercise such as qigong, yoga, and tai chi. the use of medication in the treatment of fibromyalgia is debated, although antidepressants can improve quality of life. the medications duloxetine, milnacipran, or pregabalin have been approved by the us food and drug administration (fda) for the management of fibromyalgia. other common helpful medications include serotonin-noradrenaline reuptake inhibitors (snri), non-steroidal anti-inflammatory drugs (nsaids), and muscle relaxants. q10 coenzyme and vitamin d supplements may reduce pain and improve quality of life. while fibromyalgia is persistent in nearly all patients, it does not result in death or tissue damage. fibromyalgia is estimated to affect 2–4% of the population. women are affected about twice as often as men. rates appear similar in different areas of the world and among different cultures. fibromyalgia was first defined in 1990, with updated criteria in 2011, 2016, and 2019. the term "fibromyalgia" is from neo-latin fibro-, meaning "fibrous tissues", greek μυο- myo-, "muscle", and greek άλγος algos, "pain"; thus, the term literally means "muscle and fibrous connective tissue pain". classification fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain signals are processed in the central nervous system. the international classification of diseases (icd-11) includes fibromyalgia in the category of "chronic widespread pain", code mg30.01. signs and symptoms the defining symptoms of fibromyalgia are chronic widespread pain, fatigue, and sleep disturbance. other symptoms may include heightened pain in response to tactile pressure (allodynia), cognitive problems, musculoskeletal stiffness, environmental sensitivity, hypervigilance, sexual dysfunction, and visual symptoms. pain fibromyalgia is predominantly a chronic pain disorder. according to the nhs, widespread pain is one major symptom, which could feel like: an ache, a burning sensation, or a sharp, stabbing pain. fatigue fatigue is one of the defining symptoms of fibromyalgia. patients may experience physical or mental fatigue. physical fatigue can be demonstrated by a feeling of exhaustion after exercise or by a limitation in daily activities. sleep problems sleep problems are a core symptom in fibromyalgia. these include difficulty falling asleep or staying asleep, awakening while sleeping and waking up feeling unrefreshed. a meta-analysis compared objective and subjective sleep metrics in people with fibromyalgia and healthy people. individuals with fibromyalgia had lower sleep quality and efficiency, as well as longer wake time after sleep start, shorter sleep duration, lighter sleep, and greater trouble initiating sleep when objectively assessed, and more difficulty initiating sleep when subjectively assessed. sleep problems may contribute to pain by decreased release of igf-1 and human growth hormone, leading to decreased tissue repair. improving sleep quality can help people with fibromyalgia minimize pain. cognitive problems many people with fibromyalgia experience cognitive problems (known as fibrofog or brainfog). one study found that approximately 50% of fibromyalgia patients had subjective cognitive dysfunction and that it was associated with higher levels of pain and other fibromyalgia symptoms. the american pain society recognizes these problems as a major feature of fibromyalgia, characterized by trouble concentrating, forgetfulness and disorganized or slow thinking. about 75% of fibromyalgia patients report significant problems with concentration, memory, and multitasking. a 2018 meta-analysis found that the largest differences between fibromyalgia patients and healthy subjects were for inhibitory control, memory, and processing speed. it is hypothesized that the increased pain compromises attention systems, resulting in cognitive problems. hypersensitivity in addition to a hypersensitivity to pain, patients with fibromyalgia show hypersensitivity to other stimuli, such as bright lights, loud noises, perfumes and cold. a review article found that they have a lower cold pain threshold. other studies documented an acoustic hypersensitivity. comorbidity fibromyalgia as a stand-alone diagnosis is uncommon, as most fibromyalgia patients often have other chronic overlapping pain problems or mental disorders. fibromyalgia is associated with mental health issues like anxiety, posttraumatic stress disorder, bipolar disorder, alexithymia, and depression. patients with fibromyalgia are five times more likely to have major depression than the general population. fibromyalgia and numerous chronic pain conditions frequently coexist. these include chronic tension headaches, myofascial pain syndrome, and temporomandibular disorders. multiple sclerosis, post-polio syndrome, neuropathic pain, and parkinson's disease are four neurological disorders that have been linked to pain or fibromyalgia. fibromyalgia largely overlaps with chronic fatigue syndrome and may share the same pathogenetic mechanisms. comorbid fibromyalgia has been reported to occur in 20–30% of individuals with rheumatic diseases. it has been reported in people with noninflammatory musculoskeletal diseases. the prevalence of fibromyalgia in gastrointestinal disease has been described mostly for celiac disease and irritable bowel syndrome (ibs). ibs and fibromyalgia share similar pathogenic mechanisms, involving immune system mast cells, inflammatory biomarkers, hormones, and neurotransmitters such as serotonin. changes in the gut biome alter serotonin levels, leading to autonomic nervous system hyperstimulation. fibromyalgia has also been linked with obesity. other conditions that are associated with fibromyalgia include connective tissue disorders, cardiovascular autonomic abnormalities, and an overactive bladder. risk factors the cause of fibromyalgia is unknown. however, several risk factors, genetic and environmental, have been identified. genetics genetics play a major role in fibromyalgia, and may explain up to 50% of the disease susceptibility. fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems. several genes have been suggested as candidates for susceptibility to fibromyalgia. these include slc6a4, trpv2, myt1l, nrxn3, and the 5-ht2a receptor 102t/c polymorphism. the heritability of fibromyalgia is estimated to be higher in patients younger than 50. neuropathic pain and major depressive disorder often co-occur with fibromyalgia – 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 fibromyalgia and sometimes a mood disorder. stress stress and trauma are strongly linked to fibromyalgia stress may be an important precipitating factor in the development of fibromyalgia. a 2021 meta-analysis found psychological trauma to be strongly associated with fibromyalgia. people who suffered abuse in their lifetime were three times more likely to have fibromyalgia, 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 fibromyalgia may stem from stress-induced disruption of the hpa axis. personality although some have suggested that fibromyalgia 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. other risk markers other risk markers for fibromyalgia include premature birth, female sex, cognitive influences, primary pain disorders, multiregional pain, infectious illness, hypermobility of joints, iron deficiency and small-fiber polyneuropathy. metal-induced allergic inflammation has also been linked with fibromyalgia, especially in response to nickel but also inorganic mercury, cadmium, and lead. pathophysiology as of 2022, the pathophysiology of fibromyalgia has not yet been elucidated and several theories have been suggested. pain processing abnormalities chronic pain can be divided into three categories. nociceptive pain is pain caused by inflammation or damage to tissues. neuropathic pain is pain caused by nerve damage. nociplastic pain (or central sensitization) is less understood and is the common explanation of the pain experienced in fibromyalgia. because the three forms of pain can overlap, fibromyalgia patients may experience nociceptive (e.g., rheumatic illnesses) and neuropathic (e.g., small fiber neuropathy) pain, in addition to nociplastic pain. nociplastic pain (central sensitization) fibromyalgia can be viewed as a condition of nociplastic pain. nociplastic pain is caused by an altered function of pain-related sensory pathways in the periphery and the central nervous system, resulting in hypersensitivity. nociplastic pain is commonly referred to as "nociplastic pain syndrome" because it is coupled with other symptoms. these include fatigue, sleep disturbance, cognitive disturbance, hypersensitivity to environmental stimuli, anxiety, and depression. nociplastic pain is caused by either (1) increased processing of pain stimuli or (2) decreased suppression of pain stimuli at several levels in the nervous system, or both. neuropathic pain an alternative hypothesis to nociplastic pain views fibromyalgia as a stress-related dysautonomia with neuropathic pain features. this view highlights the role of autonomic and peripheral nociceptive nervous systems in the generation of widespread pain, fatigue, and insomnia. the description of small fiber neuropathy in a subgroup of fibromyalgia patients supports the disease neuropathic-autonomic underpinning. however, others claim that small fiber neuropathy occurs only in small groups of those with fibromyalgia. autonomic nervous system some suggest that fibromyalgia is caused or maintained by a decreased vagal tone, which is indicated by low levels of heart rate variability, signaling a heightened sympathetic response. accordingly, several studies show that clinical improvement is associated with an increase in heart rate variability. some examples of interventions that increase the heart rate variability and vagal tone are meditation, yoga, mindfulness and exercise. in 2023 the fibromyalgia: imbalance of threat and soothing systems (fitss) model was suggested as a working hypothesis. according to the fitss model, the salience network (also known as the midcingulo-insular network) may remain continuously hyperactive due to an imbalance in emotion regulation, which is reflected by an overactive "threat" system and an underactive "soothing" system. this hyperactivation, along with other mechanisms, may contribute to fibromyalgia. neurotransmitters some neurochemical abnormalities that occur in fibromyalgia also regulate mood, sleep, and energy, thus explaining why mood, sleep, and fatigue problems are commonly co-morbid with fibromyalgia. serotonin is the most widely studied neurotransmitter in fibromyalgia. it is hypothesized that an imbalance in the serotoninergic system may lead to the development of fibromyalgia. there is also some data that suggests altered dopaminergic and noradrenergic signaling in fibromyalgia. supporting the monoamine related theories is the efficacy of monoaminergic antidepressants in fibromyalgia. neurophysiology neuroimaging studies have observed decreased grey matter of the default mode network in people with fibromyalgia. these deficits are associated with pain processing. neuroendocrine system studies on the neuroendocrine system and hpa axis in fibromyalgia have been inconsistent. one study found fibromyalgia patients exhibited higher plasma cortisol, more extreme peaks and troughs, and higher rates of dexamethasone non-suppression. however, other studies have only found correlations between a higher cortisol awakening response and pain, and not any other abnormalities in cortisol. increased baseline acth and increase in response to stress have been observed, hypothesized to be a result of decreased negative feedback. immune system inflammation has been suggested to have a role in the pathogenesis of fibromyalgia. people with fibromyalgia tend to have higher levels of inflammatory cytokines il-6, and il-8. there are also increased levels of the pro-inflammatory cytokines il-1 receptor antagonist. increased levels of pro-inflammatory cytokines may increase sensitivity to pain, and contribute to mood problems. anti-inflammatory interleukins such as il-10 have also been associated with fibromyalgia. a repeated observation shows that autoimmunity triggers such as traumas and infections are among the most frequent events preceding the onset of fibromyalgia. neurogenic inflammation has been proposed as a contributing factor to fibromyalgia. gut microbiome though there is a lack of evidence in this area, it is hypothesized that gut bacteria may play a role in fibromyalgia. people