Evidence browser

NeuroinflammationPain and SensitizationBiomarkersImmune System

Clinical applications of epigenetic signatures in chronic pain management and health outcome prediction.

Ben Amar, Jinane, Michiels, Joni, Hendrix, Jolien et al.·Epigenomics·2026

This review examined how epigenetic changes—chemical switches that turn genes on and off without altering DNA itself—are observed in chronic pain conditions including fibromyalgia and ME/CFS. Researchers found that alterations in DNA methylation and other epigenetic marks are associated with inflammation, pain signaling, and sensitization pathways. The review suggests that epigenetic markers may one day help identify people at risk or predict outcomes, though these applications remain preliminary and require further development.

NeuroinflammationPain and SensitizationInterventionsSleep

Multimorbidity in Chronic Overlapping Pain Conditions: From Burden to Integrated Care.

d'Incau, Emmanuel, Kaplan, Chelsea Marie, Micoulaud-Franchi, Jean-Arthur et al.·Journal of clinical medicine·2026

This evidence map examines chronic overlapping pain conditions—a group of ten disorders including fibromyalgia, migraine, irritable bowel syndrome, and ME/CFS that frequently occur together in the same patients. Researchers observed that when multiple conditions coexist, patients report greater pain, worse sleep, more fatigue, and lower quality of life, along with fragmented care across many specialists. The review proposes that integrated screening and coordinated care might help, though effectiveness of these approaches remains to be tested.

Pain and SensitizationBiomarkersDiagnosticsLong COVID Overlap

DNA methylation: unifying framework for complex chronic conditions.

Sharma, Sayan, Rodger, Euan J, Chatterjee, Aniruddha et al.·Trends in genetics : TIG·2026

This review examines how chemical tags on DNA (called DNA methylation) may help explain why ME/CFS, long COVID, fibromyalgia, and hypermobile Ehlers-Danlos syndrome share similar symptoms. The authors propose that studying these chemical changes across these related conditions could improve diagnosis and treatment. However, this is a framework paper synthesising existing evidence, not a new study proving how methylation causes these illnesses.

E0 ConsensusReviewPEM not requiredSystematic-Review

Effect of photobiomodulation on pain and quality of life in fibromyalgia syndrome: a systematic review.

G A, Swathi, Maiya, G Arun, Shetty, Shiran et al.·Lasers in medical science·2026

A systematic review of seven randomised controlled trials examined whether photobiomodulation therapy (a light-based treatment) could reduce pain and improve quality of life in fibromyalgia syndrome. The review reported short-term reductions in pain intensity and improvements in quality of life, sleep quality, and psychological well-being in study participants. However, the studies included were quite different from one another, which limits how widely these findings can be generalised; the authors note that larger, more standardised clinical trials are needed to clarify the actual role of this treatment.

Pain and SensitizationInterventionsSleep

E0 ConsensusReviewPEM unclearSystematic-Review

A systematic scoping review and conceptual analysis of new-onset fibromyalgia manifestations after non-hospitalized COVID-19: empirics, definitions, methodologies, pathophysiology, mapping of literature, and knowledge gaps.

Plaut, Shiloh·Journal of translational medicine·2026

This systematic review examined published studies on fibromyalgia-like symptoms that develop after mild COVID-19 infection. Researchers searched medical databases and found 228 studies reporting overlap between long COVID, chronic fatigue, and fibromyalgia, but noted that different studies use inconsistent definitions and methods, making it difficult to draw firm conclusions. The causes of these overlapping conditions remain unclear.

NeuroinflammationPain and SensitizationImmune SystemLong COVID Overlap

E0 ConsensusReviewPEM not requiredSystematic-Review

Effectiveness of Pain Neuroscience Education in Patients with Chronic Musculoskeletal Pain and Central Sensitization: A Systematic Review.

Lepri, Beatrice, Romani, Daniele, Storari, Lorenzo et al.·International journal of environmental research and public health·2023

This review looked at 15 studies testing whether pain neuroscience education—teaching patients how pain works in the nervous system—helps people with chronic muscle and joint pain, including those with conditions like fibromyalgia and chronic fatigue syndrome. The research found that this type of education does appear to reduce pain and improve disability and mood, especially when delivered one-on-one and combined with other treatments like physical therapy.

E0 ConsensusReviewPEM not requiredSystematic-Review

A systematic review on the health outcomes associated with non-endocarditis manifestations of chronic Q fever.

Manchal, Naveen, Adegboye, Oyelola A, Eisen, Damon P·European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology·2020

This study looked at chronic Q fever, a bacterial infection that can cause long-term complications beyond heart valve infections. Researchers found that when chronic Q fever affects bones, blood vessels, or causes abscesses (pockets of infection), patients experience significantly more pain than other forms of the disease. Importantly, the study reviewed existing research to understand how pain and fatigue appear in these less common forms of chronic Q fever.

E0 ConsensusReviewPEM unclearSystematic-Review

Interventions to treat pain in paediatric CFS/ME: a systematic review.

Ascough, Caitlin, King, Hayley, Serafimova, Teona et al.·BMJ paediatrics open·2020

This review looked at whether treatments for ME/CFS in children help reduce pain, which affects about two-thirds of young patients. Researchers searched medical databases for studies measuring pain before and after treatment. They found that most treatment studies didn't even measure pain, and the few that did weren't specifically designed to treat pain—they focused on overall ME/CFS management. The evidence suggests that children who recover from ME/CFS tend to have less pain than those who don't recover.

E0 ConsensusReviewPEM not requiredSystematic-Review

Identification of mental health and quality of life outcomes in primary care databases in the UK: a systematic review.

Carreira, Helena, Williams, Rachael, Strongman, Helen et al.·BMJ open·2019

Researchers reviewed 120 studies that used UK patient medical records to track mental health and quality of life problems like depression, anxiety, fatigue, and cognitive issues. They found that different studies used different definitions and coding systems to identify these conditions, making it hard to compare results across studies. The authors recommend that researchers agree on standard definitions and validated code lists so findings are more consistent and reliable.

Pain and SensitizationSleepCognitive Impairment

Pathophysiology of interstitial cystitis.

Birder, Lori A·International journal of urology : official journal of the Japanese Urological Association·2019

Interstitial cystitis is a chronic bladder pain condition with no clear cause and no universally accepted treatment. This review examines how bladder pain occurs without obvious damage to bladder tissue or nerves, and notes that patients with this condition often have overlapping symptoms with other chronic pain syndromes like fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome. Researchers use animal models and look for biomarkers in urine to better understand the condition and develop new treatments.

Are Traditional Remedies Useful in Management of Fibromyalgia and Chronic Fatigue Syndrome? A Review Study.

Mahjoub, Fatemeh, Salari, Roshanak, Noras, Mohammad Reza et al.·Journal of evidence-based complementary & alternative medicine·2017

This study looked at how traditional Persian medicine approaches fibromyalgia and ME/CFS, which are conditions that cause widespread pain and extreme tiredness. The researchers compared ancient Persian medical texts, particularly writings by the physician Avicenna, with modern understanding of these diseases. They found that traditional medicine recognized fatigue as a complex condition with different types, each with distinct symptoms.

E0 ConsensusGuidelinePEM not requiredGuideline

Chronic Pelvic Pain in Women.

Speer, Linda M, Mushkbar, Saudia, Erbele, Tara·American family physician·2016

Chronic pelvic pain in women is long-lasting pain in the pelvic area that lasts more than six months and often has no clear cause. This guideline explains that pelvic pain is frequently linked to other pain conditions and mental health issues like depression, and recommends a whole-person approach to treatment that combines medical care, physical therapy, and behavioral support.

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.

Walitt, Brian, Ceko, Marta, Gracely, John L et al.·Current rheumatology reviews·2016

This review examined brain imaging studies of ME/CFS and similar conditions to understand what happens in the nervous system. Researchers found that people with these conditions show increased sensitivity to pain and other sensations, suggesting these are real physical conditions—not imaginary or feigned. However, brain imaging hasn't yet revealed a single clear pattern or 'fingerprint' that all these conditions share, and we still don't know if this sensory sensitivity causes the disease or is a result of it.

Yoga intervention and functional pain syndromes: a selective review.

Sutar, Roshan, Yadav, Suresh, Desai, Geetha·International review of psychiatry (Abingdon, England)·2016

This review looked at studies examining whether yoga might help people with chronic pain conditions that are hard to diagnose, including ME/CFS. The researchers found that several studies suggested yoga may provide modest benefits for these types of pain conditions. However, more large-scale research is needed to confirm how helpful yoga really is.

E0 ConsensusReviewPEM not requiredSystematic-Review

Bladder pain syndrome/interstitial cystitis as a functional somatic syndrome.

Warren, John W·Journal of psychosomatic research·2014

This study asks whether bladder pain syndrome/interstitial cystitis (BPS/IC) is a type of functional somatic syndrome—a condition where symptoms are real but may not show up on standard tests. The researchers reviewed existing research and found that BPS/IC shares most characteristics with other functional somatic syndromes, suggesting that at least some cases of BPS/IC might work similarly to conditions like ME/CFS.

Gynecological disorders in bladder pain syndrome/interstitial cystitis patients.

Cervigni, Mauro, Natale, Franca·International journal of urology : official journal of the Japanese Urological Association·2014

This review examined how often bladder pain syndrome (chronic bladder inflammation and pain) occurs together with gynecological conditions like endometriosis and vulvodynia in women. The researchers found that these conditions frequently overlap—for example, about 48% of women with endometriosis also have bladder pain syndrome. They also found that pelvic floor muscle dysfunction is very common in bladder pain patients, affecting up to 87% of them.

Pain and SensitizationCognitive Impairment

Dysfunctional syndromes and fibromyalgia: a 2012 critical digest.

Sarzi-Puttini, Piercarlo, Atzeni, Fabiola, Di Franco, Manuela et al.·Clinical and experimental rheumatology·2012

This review looked at several long-lasting conditions that cause widespread pain, tiredness, sleep problems, and difficulty concentrating—conditions that don't always show up clearly on standard medical tests. The researchers examined fibromyalgia, ME/CFS, and irritable bowel syndrome to understand how they're connected and what causes symptoms to keep happening. They found that these conditions share similar patterns in how the nervous system processes pain and fatigue.

The prevalence of fibromyalgia in other chronic pain conditions.

Yunus, Muhammad B·Pain research and treatment·2012

This review examined how often fibromyalgia (a condition causing widespread pain and fatigue) occurs alongside other chronic pain conditions, including ME/CFS. The researchers found that fibromyalgia frequently co-occurs with conditions like rheumatoid arthritis, lupus, and osteoarthritis, and that it can be missed or misdiagnosed in people who have these other diseases. Recognizing fibromyalgia separately is important because it may change how doctors treat patients and what medications they use.

Pain and SensitizationSleep

Sleep, pain, fibromyalgia, and chronic fatigue syndrome.

Landis, Carol A·Handbook of clinical neurology·2011

This review examined the connections between sleep problems, pain, fibromyalgia, and chronic fatigue syndrome (ME/CFS). The author looked at existing research to understand how poor sleep and pain symptoms often occur together in these conditions and how they may be related to each other.

E0 ConsensusReviewPEM unclearSystematic-Review

Systematic review of multi-symptom conditions in Gulf War veterans.

Thomas, Hollie V, Stimpson, Nicola J, Weightman, Alison L et al.·Psychological medicine·2006

This review examined 23 studies comparing health problems in Gulf War veterans to people who were not deployed. Veterans who served in the Gulf War were nearly 4 times more likely to develop chronic fatigue syndrome and about 3.5 times more likely to report multiple chemical sensitivities or other multi-symptom illnesses. The review suggests that deployment to the Gulf War is connected with higher rates of these conditions.