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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,166 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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244 studies

E0 — Consensus643E1 — Replicated320E2 — Moderate2,781E3 — Preliminary2,422

ME/CFS4,025Long COVID216Post-infectious189Overlapping1,050

Required for diagnosis414Not specified / unclear2,218Not required3,534

Post-Exertional Malaise1,063Cognitive Dysfunction1,735Pain1,620Unrefreshing Sleep799Orthostatic Intolerance478

Cytokines818Gene Expression567Metabolomics473Neuroimaging468Autoantibodies458

Infection-Triggered1,174Long COVID Overlap587Pediatric493Severe231

Strong Phenotyping438Sex-Stratified326Severe ME Included118

Systematic Review265Meta-Analysis60RCT300

Peer-reviewed6,109Preprint3Unclear54

181–200 of 244 studies

E3 PreliminaryCohortPEM not requiredCase-Control

Multiple chemical sensitivity caused by exposure to ignition coal fumes: a case report.

Yun, Myeong-Ja, Kang, Dong-Mug, Lee, Kyoung-Hye et al.·Annals of occupational and environmental medicine·2013

This case report describes a 55-year-old woman who developed multiple chemical sensitivity (MCS)—a condition where exposure to everyday smells and chemicals triggers symptoms like swelling and muscle pain—after being exposed to coal fumes at work. Her symptoms started with coal fumes but gradually expanded to include reactions to city gas, burning smells, and exhaust. After careful testing ruled out other conditions, she was diagnosed with MCS and learned to avoid her triggers.

Pain and Sensitization

E3 PreliminaryMechanismPEM not requiredMechanistic

Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome.

Medow, Marvin S, Aggarwal, Arun, Baugham, Ila et al.·Journal of applied physiology (Bethesda, Md. : 1985)·2013

When skin is heated, blood vessels normally dilate to increase blood flow. This study found that people with ME/CFS have lower baseline blood flow in their skin compared to healthy people. When researchers used drugs to reduce harmful molecules called reactive oxygen species (particularly hydrogen peroxide), blood flow improved and the initial blood vessel response to heat increased in ME/CFS patients but not in healthy controls.

Pain and SensitizationAutonomic Nervous System

E3 PreliminaryReviewPEM unclearReview-Narrative

The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

Meeus, Mira, Nijs, Jo, Hermans, Linda et al.·Expert opinion on therapeutic targets·2013

This study explores how damage to the energy-producing parts of cells (mitochondria) might explain why ME/CFS and fibromyalgia patients experience persistent pain and fatigue. When the body experiences oxidative stress, it produces harmful molecules that can damage mitochondria and reduce the energy (ATP) available to muscles and the brain. The researchers suggest that boosting antioxidants and repairing mitochondria could be promising treatments worth testing.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Irritable bowel syndrome and migraine: bystanders or partners?

Chang, Full-Young, Lu, Ching-Liang·Journal of neurogastroenterology and motility·2013

This editorial examines two common chronic pain conditions—irritable bowel syndrome (IBS) and migraine—and explores whether they might be related. Both conditions are more common in women, significantly reduce quality of life, and often occur together in the same patients. The authors suggest these disorders may share underlying causes related to how the nervous system processes pain, rather than being completely separate diseases.

Pain and Sensitization

E3 PreliminaryReviewPEM not requiredReview-Narrative

Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Castori, Marco, Morlino, Silvia, Celletti, Claudia et al.·American journal of medical genetics. Part A·2013

This review examines joint hypermobility syndrome and a related condition called Ehlers-Danlos syndrome hypermobility type, which cause chronic pain, loose joints, and other symptoms like fatigue and headaches. The authors describe how these conditions develop over time and suggest that they may share similar underlying mechanisms with other chronic illnesses like ME/CFS and fibromyalgia. The goal is to help doctors better recognize and treat these conditions.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

[Back pain and somatisation].

Jenewein, Josef·Therapeutische Umschau. Revue therapeutique·2013

Back pain is common in people with somatoform disorders, where physical symptoms occur without a clear medical cause. About 10–20% of back pain patients have this type of disorder, and up to half also experience depression or anxiety. Doctors need to distinguish somatoform pain from other conditions like fibromyalgia and ME/CFS. Treatment typically involves talk therapy, relaxation techniques, physical activity, and sometimes antidepressant medications.

Pain and Sensitization

E3 PreliminaryReviewPEM not requiredReview-Narrative

Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions.

Staud, Roland·Expert review of neurotherapeutics·2012

People with chronic pain often have trouble turning off pain signals in their brain and spinal cord, even when they should. This review explains that many chronic pain conditions—including ME/CFS—share a common problem: their bodies amplify pain signals instead of suppressing them. Tests can measure how well someone's natural pain-blocking system works, and these tests might help predict who will develop chronic pain.

Pain and Sensitization

E3 PreliminaryCohortPEM not requiredObservational

Amisulpride in the treatment of fibromyalgia: an uncontrolled study.

Rico-Villademoros, Fernando, Rodriguez-Lopez, Carmen Maria, Morillas-Arques, Piedad et al.·Clinical rheumatology·2012

Researchers tested whether a medication called amisulpride, which is sometimes used to treat pain and mood problems, could help people with fibromyalgia. Over 12 weeks, 40 patients took this medication along with their regular treatments. The medication did not significantly reduce pain or other fibromyalgia symptoms, and many patients stopped taking it because of side effects.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Peripheral and central mechanisms of fatigue in inflammatory and noninflammatory rheumatic diseases.

Staud, Roland·Current rheumatology reports·2012

Fatigue in rheumatic diseases like ME/CFS, fibromyalgia, and lupus comes from both physical body problems and mental/central nervous system factors, not just one or the other. Doctors can measure physical fatigue through muscle tests and mental fatigue through questionnaires. Importantly, pain and mood problems are often stronger predictors of fatigue than the disease activity itself, and treatments for both medication and lifestyle changes can help.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

The role of antipsychotics in the management of fibromyalgia.

Calandre, Elena P, Rico-Villademoros, Fernando·CNS drugs·2012

This review examines whether antipsychotic medications—drugs typically used to treat psychiatric conditions—might also help people with fibromyalgia manage pain, sleep problems, fatigue, and mood disturbances. The authors found that some antipsychotics, particularly quetiapine, have shown promise in small studies and case reports, though most research is preliminary and more rigorous testing is needed.

Pain and SensitizationSleep

E3 PreliminaryReviewPEM unclearReview-Narrative

Temporomandibular disorders and functional somatic syndromes: deliberations for the dentist.

Suma, S, Veerendra Kumar, B·Indian journal of dental research : official publication of Indian Society for Dental Research·2012

This paper discusses jaw and joint problems (temporomandibular disorders) that commonly occur alongside conditions like ME/CFS and fibromyalgia. It explains that these jaw problems are often overlooked because they stem from increased pain sensitivity related to stress and psychological factors, rather than just physical damage. The authors argue that dentists need to recognize these connections and adjust their treatment approach for patients with these overlapping conditions.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Central sensitization as a component of post-deployment syndrome.

Lewis, Jeffrey D, Wassermann, Eric M, Chao, Wendy et al.·NeuroRehabilitation·2012

This study suggests that post-deployment syndrome—a condition affecting military veterans with chronic pain, fatigue, and memory problems—may develop through a process called central sensitization. Central sensitization means the nervous system becomes overly sensitive and amplifies pain signals. The researchers propose this happens because of changes in how the brain and spinal cord process information, and that stress and genes may increase the risk.

Pain and Sensitization

E3 PreliminaryBehavioralPEM not requiredCase-Control

Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study.

Van Oosterwijck, Jessica, Nijs, Jo, Meeus, Mira et al.·Journal of rehabilitation research and development·2011

This small study tested whether teaching patients with chronic neck pain from whiplash about how pain works in the body could help them feel better. Six patients received this education, and researchers found that afterward, patients had less fear of movement, used healthier coping strategies, reported less disability, and could move their necks with less pain.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

Nijs, Jo, Meeus, Mira, Van Oosterwijck, Jessica et al.·Expert opinion on pharmacotherapy·2011

This review examines how the nervous system can become overly sensitive to pain signals, a condition called central sensitization that occurs in many chronic pain disorders including ME/CFS. The authors summarize different treatment approaches—including medications, physical therapy, brain stimulation, and stress management—that may help calm down an overactive pain processing system in the brain and spinal cord.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Structural integration, an alternative method of manual therapy and sensorimotor education.

Jacobson, Eric·Journal of alternative and complementary medicine (New York, N.Y.)·2011

Structural Integration (SI) is a hands-on therapy that focuses on improving how your body moves and holds itself, rather than treating specific symptoms. This review looked at what we know about how SI might work—such as making muscles and connective tissues more flexible and improving how your nervous system processes movement and stress—and found that small studies have reported improvements in pain, movement, balance, and well-being in some conditions including chronic fatigue.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Idiopathic environmental intolerances (IEI): from molecular epidemiology to molecular medicine.

De Luca, C, Scordo, G, Cesareo, E et al.·Indian journal of experimental biology·2010

Some people with ME/CFS and related conditions may have difficulty processing chemicals, metals, and other substances they encounter in the environment because of inherited or acquired differences in how their bodies handle these toxins. This review suggests that genetic variations affecting enzymes responsible for detoxifying chemicals, combined with problems in the body's antioxidant systems, might explain why some people react strongly to very small amounts of environmental exposures. Understanding these biological mechanisms could help develop personalized treatments.

Pain and Sensitization

E3 PreliminaryReviewPEM not requiredReview-Narrative

Fibromyalgia syndrome: a discussion of the syndrome and pharmacotherapy.

Smith, Howard S, Barkin, Robert L·American journal of therapeutics·2010

Fibromyalgia is a condition that causes widespread pain throughout the body, along with fatigue, sleep problems, brain fog, and mood changes. This article explains that fibromyalgia may share common features with ME/CFS and other conditions involving heightened pain sensitivity. While there is no cure, doctors can help manage symptoms through exercise, therapy, patient education, and specific medications.

Pain and SensitizationSleepCognitive Impairment

E3 PreliminaryReviewPEM unclearReview-Narrative

The role of corticosteroids and stress in chronic pain conditions.

McEwen, Bruce S, Kalia, Madhu·Metabolism: clinical and experimental·2010

This review explores how stress hormones (corticosteroids) and the body's stress response system affect chronic pain conditions, including ME/CFS. The authors explain that these hormones can have surprising and contradictory effects—sometimes reducing pain, sometimes increasing it—depending on the dose and where they act in the body. They examine how chronic stress and nervous system changes in conditions like ME/CFS, fibromyalgia, and IBS may be linked to pain through brain changes and immune system activity.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

[Functional somatic syndrome in dental practice].

Inamitsu, Tetsuaki·Nihon rinsho. Japanese journal of clinical medicine·2009

Many people experience pain and discomfort in their face, jaw, and mouth that doctors and dentists cannot easily explain with standard tests. This review discusses how conditions like temporomandibular disorder (jaw pain), burning mouth syndrome, and facial pain are related to each other and to broader conditions like fibromyalgia and chronic fatigue syndrome. These conditions often occur alongside anxiety, depression, and other mental health challenges, and treating them effectively requires a team approach including medication, physical therapy, and counseling.

Pain and Sensitization

E3 PreliminaryReviewPEM unclearReview-Narrative

Fibromyalgia: pathogenetic, diagnostic and therapeutic concerns.

Podolecki, Tomasz, Podolecki, Andrzej, Hrycek, Antoni·Polskie Archiwum Medycyny Wewnetrznej·2009

Fibromyalgia is a condition causing widespread muscle and joint pain that affects many people worldwide. This review examines what we know about fibromyalgia's causes, how doctors diagnose it, and how it can be treated. The authors note that fibromyalgia likely results from multiple factors involving the nervous system, brain chemistry, and immune function, and that treatment typically involves antidepressants, therapy, and other approaches.

Pain and SensitizationDiagnostics

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.