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Pain and Sensitization

238 studies in the atlas

Chronic pain is reported by a majority of ME/CFS patients, including headaches, muscle pain, joint pain, and widespread tenderness. Central sensitization — an amplification of pain signals by the nervous system — may contribute. The overlap with fibromyalgia is substantial, though the two conditions are considered distinct.

What we know

  • Chronic pain is reported by a majority of ME/CFS patients across multiple symptom domains
  • Substantial clinical overlap exists between ME/CFS and fibromyalgia, though they have distinct diagnostic criteria
  • Central sensitization mechanisms have been proposed based on pain processing studies
  • Pain symptoms often worsen during PEM episodes

What remains uncertain

  • Whether central sensitization in ME/CFS has the same mechanisms as in fibromyalgia
  • Small fiber neuropathy may contribute to pain in a subset of patients
  • Whether pain management approaches effective in fibromyalgia also help ME/CFS patients
  • The relationship between neuroinflammation and pain sensitization in ME/CFS

What is emerging

  • Whether pain subtypes exist within ME/CFS that respond to different treatments
  • The precise overlap and distinction between ME/CFS pain and fibromyalgia pain
  • Whether pain biomarkers can help distinguish ME/CFS from other chronic pain conditions
  • The role of glial cell activation in ME/CFS pain

Start here

E0 ConsensusPEM unclearWeak / uncertain

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.

Research Momentum

238 publications over 36 years. Recent trend: decreasing (7/year over the last 3 years).

All Studies

238 studies, sorted by review status and evidence level

E0 ConsensusPEM unclearWeak / uncertainSystematic-ReviewEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

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
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM unclearModerate confidenceReview-NarrativeEditor reviewed

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.

Pain and SensitizationCognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

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 Sensitization
E0 ConsensusPEM unclearModerate confidenceSystematic-ReviewEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Genetic factors in neuromuscular pain.

Buskila, Dan, Neumann, Lily, Press, Joseph·CNS spectrums·2005

This review examined whether ME/CFS, fibromyalgia, and related chronic pain conditions share genetic roots. Researchers looked at recent studies suggesting that genes involved in serotonin and dopamine—brain chemicals that affect mood and pain—may make some people more likely to develop these conditions. The review also highlights that environmental triggers (like infections or stress) likely play a role in people who are genetically predisposed.

Pain and Sensitization
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia syndrome, idiopathic widespread persistent pain or syndrome of myalgic encephalomyelopathy (SME): what is its nature?

Mehendale, Anand W, Goldman, Mark P·Pain practice : the official journal of World Institute of Pain·2002

This review summarizes what scientists and doctors know about fibromyalgia and ME/CFS by examining research from the past 25 years. The authors looked at studies on symptoms, causes, blood test findings, brain imaging, and what patients reported about their experiences. They propose that these conditions may need to be understood in an entirely new way.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceMeta-AnalysisEditor reviewed

Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms.

Cairns, Victoria, Godwin, Jon·International journal of epidemiology·2005

This study looked at patients who had Lyme disease and found that many experienced long-lasting fatigue, muscle and joint pain, and thinking difficulties even after antibiotic treatment. Researchers combined results from five previous studies comparing Lyme disease patients to healthy controls and found these symptoms were significantly more common in the Lyme disease group. The symptom pattern was notably different from other conditions like fibromyalgia or depression.

Pain and SensitizationCognitive Impairment
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceGuidelineEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

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 Sensitization
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

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.

Pain and Sensitization
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

[What happens to the fibromyalgia syndrome?].

Maquet, D, Croisier, J L, Crielaard, J M·Annales de readaptation et de medecine physique : revue scientifique de la Societe francaise de reeducation fonctionnelle de readaptation et de medecine physique·2001

This review examined fibromyalgia, a condition causing widespread muscle and joint pain that lasts at least three months. The researchers found that fibromyalgia involves multiple problems working together: abnormal pain processing in the nervous system, poor sleep quality, muscle weakness, and hormonal imbalances. They concluded that treating fibromyalgia effectively requires a team approach addressing all these different issues, not just pain alone.

Pain and Sensitization
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Effects of Yijinjing Qigongin Alleviating Fatigue, Sleep Quality, and Health Status on Patients with Chronic Fatigue Syndrome: A Randomized, Controlled, and Parallel Group Clinical Study.

Xie, Fangfang, Dong, Wenjun, Guan, Chong et al.·Complementary medicine research·2023

This study tested whether Yijinjing, an ancient Chinese exercise practice with 12 movements, could help patients with ME/CFS. Forty patients either practiced Yijinjing six times per week for 12 weeks or received cognitive behavioral education. The Yijinjing group showed greater improvements in fatigue, sleep quality, and quality of life compared to the education group.

Pain and SensitizationSleep
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome.

Staud, Roland, Kizer, Taylor, Robinson, Michael E·Journal of pain research·2017

Researchers tested whether injecting a numbing medication (lidocaine) into muscles could help ME/CFS patients with fatigue and pain. Compared to a placebo injection, lidocaine injections did reduce fatigue more effectively, and both types of injections reduced pain, depression, and anxiety. This suggests that signals from muscles themselves may play a role in ME/CFS symptoms.

Pain and Sensitization
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a multicenter, nonblinded, randomized controlled trial.

Kim, Jung-Eun, Seo, Byung-Kwan, Choi, Jin-Bong et al.·Trials·2015

This study tested whether acupuncture—a traditional practice involving thin needles inserted into the skin—could help people with chronic fatigue syndrome (CFS) and related fatigue conditions. Researchers divided 150 patients into three groups: two received different types of acupuncture for 4 weeks along with their usual care, while one group continued usual care alone. The acupuncture groups showed some improvements in fatigue, stress, and pain compared to the usual care group.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial.

Bourke, J H, Johnson, A L, Sharpe, M et al.·Psychological medicine·2014

This study looked at whether four different ME/CFS treatments—cognitive behavioral therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT), and standard medical care—could reduce pain symptoms. Both CBT and GET appeared to reduce muscle and joint pain more than APT or standard care, though the improvements were modest in size. Importantly, these pain improvements happened independently of whether fatigue got better.

Pain and Sensitization
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial.

Oka, Takakazu, Tanahashi, Tokusei, Chijiwa, Takeharu et al.·BioPsychoSocial medicine·2014

This study tested whether a gentle form of yoga called isometric yoga could help ME/CFS patients who hadn't improved with standard treatments. Thirty patients who had tried conventional therapies for at least six months were split into two groups: one continued their usual treatment, while the other added twice-weekly yoga sessions plus daily home practice. The yoga group showed significant improvements in fatigue and some also reported pain relief, with minimal side effects.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial.

Meeus, Mira, Nijs, Jo, Van Oosterwijck, Jessica et al.·Archives of physical medicine and rehabilitation·2010

This study tested whether learning about how pain works in the nervous system could help people with ME/CFS who experience widespread pain. Researchers compared 48 patients who received either a 30-minute pain education session or standard pacing/self-management education. The group that learned about pain physiology showed better understanding of their pain and less worry and rumination about it right after the session.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceCross-SectionalEditor reviewed

Prevalence of Chronic Overlapping Pain Conditions in Participants With Chronic Low Back Pain Enrolled in a Pragmatic Trial of Mindfulness-Based Stress Reduction.

Miller, Vanessa Eve, Barnhill, Jessica, Greco, Carol M et al.·European journal of pain (London, England)·2025

This study looked at people with chronic low back pain to see how often they also have other long-term pain conditions like fibromyalgia, irritable bowel syndrome, and ME/CFS. Researchers found that 45% of people with back pain also had at least one other chronic pain condition, and these people reported more pain, fatigue, anxiety, and depression than those with back pain alone. The study suggests that chronic pain conditions often occur together and may share similar underlying causes.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study.

Hermans, Linda, Nijs, Jo, Calders, Patrick et al.·Pain practice : the official journal of World Institute of Pain·2018

This study tested whether morphine and naloxone (a drug that blocks opioid effects) change how pain is processed in people with ME/CFS, fibromyalgia, rheumatoid arthritis, and healthy controls. Researchers measured pain sensitivity and pain relief in response to these medications using pressure tests and ischemic pain. They found that morphine slightly reduced pain sensitivity in patient groups similarly to placebo, but neither morphine nor naloxone significantly changed how the body's natural pain-relief system worked.

Pain and Sensitization
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

A Randomized, Controlled Trial of Wholistic Hybrid Derived From Eye Movement Desensitization and Reprocessing and Emotional Freedom Technique (WHEE) for Self-Treatment of Pain, Depression, and Anxiety in Chronic Pain Patients.

Benor, Daniel, Rossiter-Thornton, John, Toussaint, Loren·Journal of evidence-based complementary & alternative medicine·2017

This small pilot study tested whether a self-help technique called WHEE (combining eye movements with tapping) could help people with chronic pain, depression, and anxiety. Twenty-four patients with chronic pain conditions (including 17 with ME/CFS or fibromyalgia) were split into two groups: one received WHEE treatment for 6 weeks while the other waited. The WHEE group showed improvements in anxiety and depression compared to those who waited, and when the waiting group later tried WHEE, they also experienced less pain and depression.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceObservationalEditor reviewed

Kinesiophobia and maladaptive coping strategies prevent improvements in pain catastrophizing following pain neuroscience education in fibromyalgia/chronic fatigue syndrome: An explorative study.

Malfliet, Anneleen, Van Oosterwijck, Jessica, Meeus, Mira et al.·Physiotherapy theory and practice·2017

This study looked at why some people with ME/CFS and fibromyalgia benefit more from a type of pain education (called pain neuroscience education) than others. The researchers found that patients who were very afraid of movement or who tended to worry a lot about their pain showed less improvement in their catastrophic thinking about pain after receiving this education. This suggests that for some patients, education alone may not be enough—they might need additional support to address their fears and worries.

Pain and SensitizationCognitive Impairment
E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial.

Meeus, Mira, Ickmans, Kelly, Struyf, Filip et al.·Pain physician·2013

This study tested whether acetaminophen (Tylenol) could help improve how the body's natural pain-blocking systems work in people with ME/CFS combined with fibromyalgia, compared to people with rheumatoid arthritis and healthy people. Researchers measured pain responses before and after taking acetaminophen or a placebo. The results were mixed: acetaminophen slightly helped pain thresholds in ME/CFS patients but actually made things slightly worse in arthritis patients and healthy controls, suggesting the drug affects different people very differently.

Pain and Sensitization
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Efficacy of aquatic vs land-based therapy for pain management in women with fibromyalgia: a randomised controlled trial.

Rivas Neira, S, Pasqual Marques, A, Fernández Cervantes, R et al.·Physiotherapy·2024

This study compared two types of exercise therapy for women with fibromyalgia: exercising in a pool (aquatic therapy) versus exercising on land. Both groups did 60-minute exercise sessions three times a week for 12 weeks. Six weeks after the program ended, women who did aquatic therapy reported less pain and better sleep quality than those who exercised on land, suggesting that water-based exercise may be particularly helpful for fibromyalgia.

Pain and SensitizationSleep
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Chronic Pain Prevalence, Characteristics, and Impact in United States Adults With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Adamowicz, Jenna L, Sirotiak, Zoe, Lendvai, Dora et al.·Pain management nursing : official journal of the American Society of Pain Management Nurses·2026

This study looked at how common chronic pain is in people with ME/CFS and how it affects their lives. Researchers found that about 7 out of 10 people with ME/CFS also experience chronic pain lasting months or longer. People with both ME/CFS and chronic pain reported more depression, anxiety, and difficulty with daily activities compared to people who only have chronic pain.

Pain and Sensitization
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

The association of fatigue and pain with cognitive test performance in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Oosterman, Joukje M, van der Schaaf, Marieke, de Kleijn, Willemien P E et al.·Journal of psychosomatic research·2025

This study looked at how fatigue and pain affect thinking and memory problems in people with ME/CFS. Researchers tested 1,375 patients on tasks like reaction time and attention, and found that both fatigue severity and pain severity were linked to worse cognitive performance. The effects were stronger in older patients, suggesting that age may play a role in how much fatigue and pain impact thinking abilities.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact on Quality of Life (QoL) of Persons with ME/CFS.

Muirhead, Nina L, Vyas, Jui, Ephgrave, Rachel et al.·Medicina (Kaunas, Lithuania)·2024

This study surveyed 876 people with ME/CFS from 26 countries to understand how the condition affects their daily lives. People with ME/CFS reported very poor quality of life, with an average health rating of 36 out of 100. The most common problems were difficulty doing everyday activities (97%), pain (92%), and trouble with movement (83%).

Pain and Sensitization
E2 ModeratePEM requiredModerate confidenceCross-SectionalEditor reviewed

Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome.

Sanchez, Victor, Kim, Colin K, Locatelli, Elyana V T et al.·Clinical & experimental ophthalmology·2024

Researchers studied eye dryness and discomfort in Gulf War veterans with ME/CFS and compared them to veterans without the condition. They found that people with ME/CFS reported significantly more eye pain and dryness symptoms, even though physical examination of their eyes showed similar amounts of tear production and surface damage as the control group. This suggests that the eye pain experienced by ME/CFS patients may come from causes beyond just dry eyes.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

The Significance of Pain Drawing as a Screening Tool for Cervicogenic Headache and Associated Symptoms in Chronic Fatigue.

Bernhoff, Gabriella, Huhmar, Helena M, Rasmussen-Barr, Eva et al.·Journal of pain research·2022

This study looked at whether a simple drawing tool could help identify a specific type of headache (cervicogenic headache) in people with ME/CFS. Researchers found that 42% of ME/CFS patients had a particular pain pattern on their drawings that suggested their headache came from their neck. Patients with this neck-related pain pattern also experienced more dizziness, worse pain, and lower quality of life compared to others.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceMethods-PaperEditor reviewed

Assessing sleep and pain among adults with myalgic encephalomyelitis/chronic fatigue syndrome: psychometric evaluation of the PROMIS® sleep and pain short forms.

Yang, Manshu, Keller, San, Lin, Jin-Mann S·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation·2022

This study tested whether two questionnaires (PROMIS scales) accurately measure sleep problems and pain in people with ME/CFS. Researchers surveyed over 600 ME/CFS patients and 338 healthy people at seven clinics across the USA. The questionnaires worked well—they consistently measured what they were supposed to measure, and they clearly showed the difference between ME/CFS patients (who had worse sleep and pain) and healthy controls.

Pain and SensitizationSleep
E2 ModeratePEM unclearPreliminaryLongitudinalEditor reviewed

Impact of Life Stressors on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms: An Australian Longitudinal Study.

Balinas, Cassandra, Eaton-Fitch, Natalie, Maksoud, Rebekah et al.·International journal of environmental research and public health·2021

This Australian study followed 36 ME/CFS patients over five months to see how life stressors affected their symptoms. The researchers found that major life changes like work disruptions or money problems were linked to worsening symptoms like brain fog, stomach issues, pain, and sleep problems. Interestingly, patients who had better access to healthcare and support services experienced fewer severe symptoms.

Pain and SensitizationSleep
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia.

Krumina, Angelika, Vecvagare, Katrine, Svirskis, Simons et al.·Medicina (Kaunas, Lithuania)·2021

This study looked at 65 people with ME/CFS in Latvia to understand their main symptoms and how the condition differs from simple tiredness. Researchers found that people with ME/CFS commonly experience fatigue, muscle pain, joint pain, and sleep problems—more often than people without ME/CFS. When patients had other health conditions alongside ME/CFS, their symptoms tended to be more severe.

Pain and SensitizationSleepDiagnostics
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study.

Josev, Elisha K, Cole, Rebecca C, Scheinberg, Adam et al.·Journal of clinical medicine·2021

This study followed Australian teenagers with ME/CFS for about two years after diagnosis to see how they were doing. While many young people improved in mood and some symptoms, fatigue, pain, and overall quality of life stayed significantly worse compared to healthy teenagers. About two-thirds of the teens still had ME/CFS at follow-up, suggesting the condition often persists in the early years after diagnosis.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

High Prevalence of Perineural Cysts in Patients with Fibromyalgia and Chronic Fatigue Syndrome.

Hulens, Mieke, Bruyninckx, Frans, Dankaerts, Wim et al.·Pain medicine (Malden, Mass.)·2021

Researchers found that small fluid-filled sacs called perineural cysts (Tarlov cysts) near nerve roots in the spine were present in 39% of patients diagnosed with fibromyalgia or ME/CFS—three times more common than in the general population. These cysts may irritate nerves and could potentially explain why some patients with these conditions experience widespread pain and fatigue. This finding suggests that fibromyalgia, ME/CFS, and symptomatic Tarlov cysts might share a similar underlying cause related to spinal fluid pressure.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study.

Eaton-Fitch, N, Johnston, S C, Zalewski, P et al.·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation·2020

This Australian study of 480 people with ME/CFS found that the condition severely impacts quality of life across all major areas—physical functioning, emotional well-being, pain, and energy levels. People with ME/CFS scored much lower on quality of life measures compared to the general population, with the lowest scores for physical activities and fatigue. The study identified specific symptoms like cognitive difficulties, sleep problems, and cardiovascular issues that are most strongly linked to reduced quality of life.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Longitudinal outcomes associated with significant other responses to chronic fatigue and pain.

Schmaling, Karen B, Fales, Jessica L, McPherson, Sterling·Journal of health psychology·2020

This study followed 68 people with chronic fatigue (some also with fibromyalgia) for 18 months to see how their loved ones' responses affected their health outcomes. The researchers found that when significant others responded negatively to fatigue and pain, patients experienced more pain, worse mental health, and worse fatigue symptoms over time. Interestingly, when loved ones were more helpful and comforting (solicitous), patients with more fibromyalgia tender points tended to have this response, and when loved ones helped distract patients, mental health was better.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study in Patients and Healthy Subjects.

Polli, Andrea, Van Oosterwijck, Jessica, Nijs, Jo et al.·Clinical therapeutics·2019

This study looked at whether oxidative stress (cellular damage from normal metabolism) is related to pain in ME/CFS patients, and how it connects to the vagus nerve, which helps control the body's relaxation response. Researchers had ME/CFS patients and healthy people do a mild exercise test and measured their pain, oxidative stress levels, and nerve activity before and after. They found that oxidative stress was linked to pain in ME/CFS patients, but unlike healthy people, ME/CFS patients didn't show improvements in pain or oxidative stress after exercise.

Pain and SensitizationAutonomic Nervous System
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Pain is associated with reduced quality of life and functional status in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Strand, Elin Bolle, Mengshoel, Anne Marit, Sandvik, Leiv et al.·Scandinavian journal of pain·2019

This study compared 87 ME/CFS patients with 94 healthy people to understand how pain affects quality of life. Researchers found that ME/CFS patients experience significantly more pain, anxiety, and depression, and have lower quality of life than healthy controls. Within the ME/CFS group, pain was strongly linked to reduced physical functioning and overall quality of life, suggesting that managing pain could help improve how well patients function daily.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Castro-Marrero, Jesús, Zaragozá, Maria C, González-Garcia, Sergio et al.·Journal of sleep research·2018

This study looked at sleep problems in 1,455 Spanish ME/CFS patients and found that nearly all of them reported poor sleep quality that wasn't refreshing, even when they slept. The researchers discovered that poor sleep was strongly linked to worse pain, fatigue, anxiety, depression, and lower quality of life overall. Several factors—including pain intensity, mood problems, fibromyalgia, and autonomic nervous system dysfunction—were particularly associated with sleep difficulties.

Pain and SensitizationSleepAutonomic Nervous System
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Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.

van der Schaaf, Marieke E, De Lange, Floris P, Schmits, Iris C et al.·Biological psychiatry·2017

This study examined brain structure in 89 women with ME/CFS using brain imaging. Researchers found that the amount of pain a patient experiences—not fatigue—was the strongest predictor of changes in a specific brain region called the dorsolateral prefrontal cortex. People with more pain showed smaller brain volume and lower levels of brain chemicals in this region, even after accounting for fatigue, depression, and physical activity.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Specialist treatment of chronic fatigue syndrome/ME: a cohort study among adult patients in England.

Collin, Simon M, Crawley, Esther·BMC health services research·2017

This study looked at how 952 ME/CFS patients fared after receiving treatment at 11 specialist NHS clinics in England. One year after starting treatment, about 27% felt much better, 37% felt a little better, but 20% felt the same or worse. Even 2-5 years later, 85% of patients still had ME/CFS symptoms, showing that this is a long-lasting condition that often continues despite specialist care.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Binocular Vision in Chronic Fatigue Syndrome.

Godts, Daisy, Moorkens, Greta, Mathysen, Danny G P·The American orthoptic journal·2016

This study found that people with ME/CFS have differences in how their eyes work together compared to healthy people. Specifically, ME/CFS patients had weaker ability to focus both eyes on nearby objects, reduced eye convergence (bringing eyes together to focus), and a smaller range of accommodation (adjusting focus from far to near). The researchers suggest that ME/CFS patients may benefit from reading glasses or vision exercises earlier than other people.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Pain in people with chronic fatigue syndrome/myalgic encephalomyelitis: the role of traumatic stress and coping strategies.

Krzeczkowska, Anna, Karatzias, Thanos, Dickson, Adele·Psychology, health & medicine·2015

This study looked at pain in people with ME/CFS and how they cope with it. Researchers compared 27 people with ME/CFS to 27 healthy people and found that those with ME/CFS experienced more pain and had different coping strategies. People with ME/CFS who had severe pain were less likely to use helpful coping methods like accepting their situation or thinking positively about it.

Pain and Sensitization
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A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS.

Zdunek, Maria, Jason, Leonard A, Evans, Meredyth et al.·International journal of psychology and behavioral sciences·2015

This study compared ME/CFS symptoms and disability between patients in the United States and the United Kingdom to see if the illness looks different depending on where people live. Researchers found that UK patients reported more mental health problems, pain, memory/concentration issues, and immune symptoms, while US patients more often experienced sudden illness onset and attributed their illness to physical causes. The study suggests that ME/CFS may present somewhat differently across these two countries.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

The Process of Change in Pain During Cognitive-Behavior Therapy for Chronic Fatigue Syndrome.

Bloot, Lotte, Heins, Marianne J, Donders, Rogier et al.·The Clinical journal of pain·2015

This study looked at how cognitive-behavioral therapy (CBT)—a talk therapy that helps change thoughts and behaviors—reduces pain in ME/CFS patients. Researchers followed 142 patients over the course of their treatment and found that pain and fatigue tend to improve together. The improvement in pain appeared to be partly explained by patients doing more physical activity and thinking less about their symptoms, though other factors also played a role.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis.

Wilson, Rachel L, Paterson, Kevin B, Hutchinson, Claire V·Perception·2015

This study tested whether people with ME/CFS experience more visual discomfort when looking at certain patterns compared to healthy people. Forty participants (20 with ME/CFS and 20 without) viewed three different striped patterns and reported how distorted or uncomfortable they looked. People with ME/CFS reported significantly more visual distortion, especially when viewing medium-frequency patterns, suggesting their eyes and brains may process visual information differently.

Pain and SensitizationBiomarkers
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Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study.

Winger, Anette, Kvarstein, Gunnvald, Wyller, Vegard Bruun et al.·BMJ open·2014

This study looked at pain in teenagers with ME/CFS compared to healthy teenagers. Teenagers with ME/CFS experienced more pain overall, in more places (headaches, stomach, muscles, and joints), and had lower pain thresholds—meaning their bodies reacted to pressure more sensitively. The researchers found that pain significantly interfered with daily activities in those with ME/CFS.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceLongitudinalEditor reviewed

Treatment outcome in adults with chronic fatigue syndrome: a prospective study in England based on the CFS/ME National Outcomes Database.

Crawley, E, Collin, S M, White, P D et al.·QJM : monthly journal of the Association of Physicians·2013

This study tracked over 800 people with ME/CFS who received care at NHS specialist services in England for 8-20 months. Patients showed meaningful improvements in fatigue, physical function, anxiety, depression, and pain. The study found that patients who started with more severe fatigue, disability, or pain tended to have less improvement, suggesting baseline severity is an important predictor of how well someone will improve with specialist care.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Self-critical perfectionism and its relationship to fatigue and pain in the daily flow of life in patients with chronic fatigue syndrome.

Kempke, S, Luyten, P, Claes, S et al.·Psychological medicine·2013

This study looked at whether a personality trait called self-critical perfectionism—the tendency to be harshly self-critical and set unrealistic standards—might be linked to daily fatigue and pain in ME/CFS patients. Over 14 days, 90 patients recorded their fatigue and pain levels each day. The researchers found that patients who scored higher on self-critical perfectionism did experience more fatigue and pain during the study period, even after accounting for mood differences.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive performance is of clinical importance, but is unrelated to pain severity in women with chronic fatigue syndrome.

Ickmans, Kelly, Meeus, Mira, Kos, Daphne et al.·Clinical rheumatology·2013

This study looked at whether cognitive problems (thinking, memory, attention) in women with ME/CFS are related to pain severity. Researchers gave cognitive tests and questionnaires to 29 women with ME/CFS and 17 healthy women. They found that cognitive problems were NOT linked to pain levels, but were connected to fatigue and mental health, suggesting that cognitive difficulties in ME/CFS may work differently than in other chronic pain conditions.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study.

Meeus, Mira, Nijs, Jo, Van Mol, Evelyne et al.·Clinical rheumatology·2012

This study looked at 103 people with ME/CFS who also experience widespread muscle pain, and examined how psychological factors like catastrophizing (expecting the worst), depression, and fear of movement affect their pain levels and daily activities. Over 6-12 months, the researchers found that catastrophizing and depression were the strongest predictors of both pain intensity and difficulty with daily functioning. The findings suggest that addressing these psychological factors alongside physical symptoms may be important for managing pain in ME/CFS.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies.

Ravindran, Murugan, Adewuyi, Oluwatoyin, Zheng, Yin et al.·Global journal of health science·2012

Many people with ME/CFS experience shortness of breath, but this study found that their lungs work normally—the problem isn't with how well air moves in and out. Instead, people with ME/CFS seem to be overly sensitive to physical sensations like rapid heartbeat, chest pain, and dizziness during exertion, which makes them feel breathless. This suggests the shortness of breath in ME/CFS comes from how the nervous system processes these sensations rather than from damaged lungs.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies.

Ravindran, Murugan K, Zheng, Yin, Timbol, Christian et al.·BMC neurology·2011

This study found that headaches—especially migraines—are much more common in people with ME/CFS than in healthy people. Researchers studied two groups and found that 84% of people with ME/CFS experienced migraines, compared to only 5% of healthy controls. People with ME/CFS who had migraines with visual symptoms (aura) showed more severe dizziness, memory problems, and heart-related symptoms than those without aura.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Adolescent offspring of mothers with chronic fatigue syndrome.

Smith, Mark S, Buchwald, Dedra S, Bogart, Andy et al.·The Journal of adolescent health : official publication of the Society for Adolescent Medicine·2010

This study looked at whether teenagers whose mothers have ME/CFS are more likely to develop ME/CFS themselves or experience fatigue and other related symptoms. Researchers compared 26 teenagers with mothers who had ME/CFS to 45 teenagers whose mothers were healthy. While teenagers with affected mothers showed higher rates of prolonged fatigue and ME/CFS diagnosis, the differences were small and not statistically proven.

Pain and SensitizationSleep
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study.

Meeus, Mira, Nijs, Jo, Huybrechts, Sven et al.·Clinical rheumatology·2010

This study tested whether people with ME/CFS feel pain more intensely than healthy people, even in areas where they don't typically experience pain. Researchers measured how much pressure patients and healthy volunteers could tolerate before feeling pain. They found that ME/CFS patients with chronic pain had significantly lower pain thresholds everywhere on their body, suggesting their nervous system may be in a heightened state of sensitivity.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Phenotypes of chronic fatigue syndrome in children and young people.

May, Margaret, Emond, Alan, Crawley, Esther·Archives of disease in childhood·2010

Researchers studied 333 children and young people with ME/CFS to see if the illness presents differently in different people. They found three main patterns: one involving muscle and joint pain, another involving migraine-like symptoms with sensitivity to light and sound, and a third involving sore throat and swollen lymph nodes. These different patterns were linked to varying levels of severity, suggesting that ME/CFS affects children in different ways.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy.

Crawley, E, Sterne, J A C·Archives of disease in childhood·2009

This study looked at how often children with ME/CFS attended school and how their physical abilities changed over time. Researchers found that 62% of children attended school 40% of the time or less, and those with better physical function were more likely to go to school. The study suggests that improving school attendance should focus on treatments that reduce fatigue and pain, not treatments for anxiety.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome.

Torres-Harding, Susan, Sorenson, Matthew, Jason, Leonard et al.·Journal of applied biobehavioral research·2008

This study looked at cortisol, a stress hormone, in 108 people with ME/CFS to see if abnormal cortisol levels were connected to symptoms like fatigue and pain. The researchers found that people with unusual cortisol patterns—especially those who didn't show the normal daily rise and fall—reported higher levels of fatigue. While abnormal cortisol appears linked to some ME/CFS symptoms, scientists still aren't sure whether this hormonal change causes the illness or results from it.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Chronic fatigue syndrome in children aged 11 years old and younger.

Davies, S, Crawley, E·Archives of disease in childhood·2008

This study looked at young children under age 12 with ME/CFS at a specialist clinic in Bath, UK. The researchers found that even very young children (including one as young as 2 years old) can have ME/CFS and experience severe disability, with symptoms almost identical to those seen in teenagers. Children in this age group attended school only about 40% of the time on average and reported high levels of fatigue and pain.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study.

Meeus, Mira, Nijs, Jo, Van de Wauwer, Naomi et al.·Pain·2008

This study tested how quickly the body's natural pain-blocking system kicks in when ME/CFS patients experience heat pain compared to healthy people. Researchers immersed participants' arms in warm water and tracked pain levels over time. They found that people with ME/CFS have stronger pain sensations overall, and their bodies take longer to activate the natural pain-suppression mechanism that normally reduces pain during ongoing stimulation.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing.

Nijs, Jo, Van de Putte, Karen, Louckx, Fred et al.·Pain medicine (Malden, Mass.)·2008

This study looked at 36 women with ME/CFS who experience widespread pain to understand how their thoughts about pain (called 'pain catastrophizing'—expecting the worst and feeling helpless) relate to their actual pain levels, ability to exercise, and daily functioning. Researchers found that negative thinking patterns about pain were strongly connected to how much bodily pain patients reported and how much their condition limited their activities. The study suggests that addressing these thought patterns might be an important part of managing ME/CFS with pain.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome.

Ullrich, Philip M, Afari, Niloofar, Jacobsen, Clemma et al.·Pain medicine (Malden, Mass.)·2007

This study compared identical twins where one had ME/CFS and one did not to understand pain sensitivity. Researchers tested how twins responded to cold pain and found that while people with ME/CFS reported significantly higher levels of pain and fatigue during the test, their actual physical pain thresholds were not substantially different from their unaffected twins. This suggests that the pain experience in ME/CFS may be more about how the brain perceives and processes pain rather than a difference in the body's basic pain detection system.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Reliability of physiological, psychological, and cognitive variables in chronic fatigue syndrome.

Wallman, Karen E, Morton, Alan R, Goodman, Carmel et al.·Research in sports medicine (Print)·2005

Researchers tested whether measurements of fatigue, mood, thinking ability, and physical performance in ME/CFS patients were reliable when checked weekly over four weeks. Most measurements were reliable and consistent, but fatigue ratings—both mental and physical—varied too much week-to-week to be fully trusted. Interestingly, how well people performed during exercise didn't match up well with their reported depression or mood, suggesting the problem may be in how the brain processes fatigue rather than actual muscle weakness.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome.

Vecchiet, Jacopo, Cipollone, Francesco, Falasca, Katia et al.·Neuroscience letters·2003

This study compared 21 people with ME/CFS to 20 healthy people and found that those with ME/CFS had signs of increased cellular damage (oxidative stress) and lower levels of protective molecules in their blood. People with ME/CFS also had more fatigue and their muscles were more sensitive to pain. The researchers found that the amount of cellular damage correlated with how fatigued people felt and how sensitive their muscles were.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A tender sinus does not always mean rhinosinusitis.

Naranch, K, Park, Y-J, Repka-Ramirez, M S et al.·Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery·2002

This study measured how sensitive people's sinuses and skin are to pressure pain across different groups: healthy people, those with sinus infections or allergies, and people with ME/CFS. The researchers found that people with ME/CFS had much more sensitive sinuses and skin overall compared to healthy people, suggesting that ME/CFS causes widespread pain sensitivity rather than actual sinus infection.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Multiple chemical sensitivity and chronic fatigue syndrome in British Gulf War veterans.

Reid, S, Hotopf, M, Hull, L et al.·American journal of epidemiology·2001

This study looked at how often ME/CFS and multiple chemical sensitivity (MCS—a condition where people react badly to everyday chemicals) occurred in British military personnel who served in the Gulf War. Researchers compared three groups: those deployed to the Gulf, those sent to Bosnia, and those who served during the Gulf War period but weren't deployed. They found that both conditions were more common in Gulf veterans, and MCS was strongly linked to pesticide exposure.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Self-reported sensitivity to chemical exposures in five clinical populations and healthy controls.

Nawab, S S, Miller, C S, Dale, J K et al.·Psychiatry research·2000

This study asked 225 people—including those with ME/CFS, SAD, and other conditions, plus healthy volunteers—to report how sensitive they are to everyday chemical exposures like perfumes, cleaning products, and other odors. People with ME/CFS reported significantly higher chemical sensitivity than healthy controls, and women reported more sensitivity than men. The researchers suggest that chemical sensitivity may be connected to how the body's stress-response system (the HPA axis) functions.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome.

Morriss, R K, Ahmed, M, Wearden, A J et al.·Journal of affective disorders·1999

This study looked at whether depression makes ME/CFS symptoms worse. Researchers compared three groups: ME/CFS patients without depression, ME/CFS patients with depression, and people with depression alone. They found that depression did not increase pain, headaches, or other unexplained symptoms in ME/CFS patients, but it did make their social life more difficult.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome.

Whelton, C L, Salit, I, Moldofsky, H·The Journal of rheumatology·1992

This study compared sleep patterns, virus exposure, and symptoms in 14 ME/CFS patients versus 12 healthy people. Patients reported sleep that didn't feel refreshing and had unusual brain wave patterns during sleep, but didn't show excessive daytime sleepiness. The study found no evidence that a chronic Epstein-Barr virus infection was causing the illness, but patients did have more widespread pain, tender points, and depression symptoms.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Altered Pain Perception and Modulation in Individuals With Post-COVID-Condition: Insights From Quantitative Sensory Testing.

Lange, Hannah, Reichert, Julian, Vock, Stephanie et al.·European journal of pain (London, England)·2026

This study tested how people with long COVID perceive and respond to pain compared to healthy people. Researchers applied pressure to participants' legs and measured when they first felt pain and when pain became unbearable. People with long COVID felt pain at lower pressure levels and their pain got worse more quickly than healthy controls, suggesting their nervous systems process pain differently.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Low-dose Naltrexone Improves post-COVID-19 condition Symptoms.

Tamariz, Leonardo, Bast, Elizabeth, Klimas, Nancy et al.·Clinical therapeutics·2024

This study looked at whether treatments used for ME/CFS could help people with long COVID. Researchers reviewed records from 108 patients who tried different treatments including low-dose naltrexone, amitriptyline, duloxetine, and physical therapy. They found that patients taking low-dose naltrexone were about 5 times more likely to improve compared to those doing physical therapy alone, with improvements in both fatigue and pain.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome.

Janbazi, Lobaneh, Kazemian, Alireza, Mansouri, Kourosh et al.·American journal of physical medicine & rehabilitation·2022

Researchers followed 157 people who were hospitalized with COVID-19 and checked on them 12 months later. They found that about 27% still had chronic fatigue and muscle weakness, and about 15% experienced chronic pain, mostly in the lower back and legs. Women were more likely than men to report these symptoms, and many patients were only using pain medications rather than receiving rehabilitation or mental health support.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Saini, Urvi, Aggen, Steven H, Oldehinkel, Albertine J et al.·BMC psychiatry·2026

This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome overlap in over 100,000 people. Researchers found that these conditions share common symptoms like fatigue, sleep problems, and difficulty concentrating—which they call 'general malaise'—rather than being completely separate diseases. Understanding these shared symptoms may help explain why people often have multiple conditions at the same time.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Increased Disease Burden in Irritable Bowel Syndrome With Comorbid Conditions and Psychiatric Diagnoses in a Multinational European Cohort: Results From the DISCOvERIE Project.

Midenfjord, Irina, Khadija, Mahrukh, Sundelin, Elias et al.·United European gastroenterology journal·2026

This study looked at 607 patients with irritable bowel syndrome (IBS) across nine European centers to understand how other conditions—like anxiety, depression, fibromyalgia, and chronic fatigue syndrome—affect their symptoms and overall health. Patients who had IBS along with one or more of these comorbid conditions experienced more severe digestive symptoms, mood problems, and fatigue than those with IBS alone. The more comorbidities someone had, the worse their symptoms became.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort.

Powers, John P, McIntee, Tomas J, Bhatia, Abhishek et al.·Communications medicine·2025

Researchers compared medical records from millions of patients to see how Long COVID (PASC) and ME/CFS are similar and different. They found that both conditions share common symptoms like fatigue, breathing difficulties, and trouble concentrating, but Long COVID tends to have more heart and lung problems, while ME/CFS more often involves pain and sleep issues. These similarities suggest that some treatment approaches might help both conditions.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment.

Smith, Steven J, Smith, B Holly, Sichlau, Michael J et al.·Phlebology·2025

This study looked at 45 women with chronic pelvic pain caused by abnormal blood pooling in pelvic veins. These patients experienced many symptoms beyond pelvic pain—including brain fog, fatigue, migraines, constipation, and anxiety. After receiving a catheter-based procedure to fix the blood pooling, most of these systemic symptoms improved significantly (by 50% or more).

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment
E2 ModeratePEM requiredPreliminaryCross-SectionalEditor reviewed

Exploratory study on autoantibodies to arginine-rich human peptides mimicking Epstein-Barr virus in women with post-COVID and myalgic encephalomyelitis/chronic fatigue syndrome.

Hoheisel, Friederike, Fleischer, Kathrin Maria, Rubarth, Kerstin et al.·Frontiers in immunology·2025

This study looked for certain antibodies in the blood of women with post-COVID and ME/CFS that might mistakenly attack the body's own proteins. The researchers found that patients with these conditions had more of these problematic antibodies than healthy people, and these antibodies were linked to common ME/CFS symptoms like fatigue, brain fog, pain, and autonomic problems. The results suggest that a virus (EBV) may trigger the immune system to attack human proteins that look similar to viral proteins.

Pain and SensitizationAutonomic Nervous SystemCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Network structure of functional somatic symptoms.

Litzenburger, Alexandra, Rothacher, Yannick, Hanusch, Kay-Uwe et al.·Journal of psychosomatic research·2025

This study looked at how symptoms cluster together in people with functional somatic syndromes (like ME/CFS, fibromyalgia, and others). Researchers surveyed over 3,000 young adults and used network analysis to map which symptoms tend to appear together. They found that fatigue and depression are particularly important symptoms that connect different symptom groups, and identified ten distinct clusters of related symptoms.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic-abdominal pain: A cross-sectional survey.

Bartley, Emily J, Alappattu, Meryl J, Manko, Kelsey et al.·Women's health (London, England)·2024

This study looked at 525 women with chronic pelvic and abdominal pain to understand how endometriosis (a condition where tissue grows outside the uterus) affects their pain experience. Women with endometriosis reported more severe pain, greater interference with daily life, and were more likely to have other overlapping pain conditions like fibromyalgia and chronic fatigue syndrome. The more pain conditions a woman had, the worse her overall pain burden became, regardless of whether she had endometriosis.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study.

Haider, Saman, Janowski, Adam J, Lesnak, Joseph B et al.·Pain·2023

This study surveyed 707 people with post-COVID-19, fibromyalgia, and/or ME/CFS to compare their symptoms. Researchers found that all three conditions share similar patterns of pain, fatigue, brain fog, anxiety, and depression that impact daily life. People with post-COVID-19 reported somewhat less severe pain and fatigue than those with fibromyalgia or ME/CFS, but those with multiple diagnoses had worse symptoms overall.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM requiredPreliminaryEditor reviewed

Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients.

Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Barth, Markus et al.·Frontiers in neuroscience·2023

Researchers used advanced MRI scans to examine a part of the brain called the brainstem in patients with ME/CFS and long COVID, comparing them to healthy people. They found that both patient groups had larger volumes in certain brainstem areas compared to healthy controls. The size of specific brainstem regions also correlated with symptom severity, particularly pain and breathing difficulties.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship.

Mckay, Pamela G, Martin, Colin R, Walker, Helen et al.·British journal of pain·2021

This study compared people with ME/CFS and fibromyalgia (FM) to see if these two conditions share similar symptoms and severity. Researchers asked 208 participants from each group to complete questionnaires about their pain, fatigue, sleep quality, mood, and how much these symptoms affected their daily lives. The study found that both groups experienced similarly debilitating symptoms and poor quality of life, suggesting these conditions may be connected in important ways.

Pain and SensitizationSleep
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

The impact of COVID-19 stress on pain and fatigue in people with and without a central sensitivity syndrome.

Koppert, Tim Y, Jacobs, Johannes W G, Lumley, Mark A et al.·Journal of psychosomatic research·2021

This study looked at whether pandemic-related stress made pain and fatigue worse in people with central sensitivity syndromes (conditions like ME/CFS and fibromyalgia) compared to those without these conditions. Researchers surveyed Dutch participants before COVID-19 (2018) and during the pandemic peak (2020), measuring stress levels, symptom severity, and psychological flexibility (the ability to adapt to difficult emotions). Surprisingly, the study found that while stress and symptom severity were generally linked, having a central sensitivity syndrome did not make people more vulnerable to stress-related symptom worsening.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Do patients with central sensitivity syndromes have poor subjective outcomes despite anatomical cure from pelvic organ prolapse surgery?

Vij, Monika, Dua, Anu, Davies, Anthony et al.·International urogynecology journal·2021

This study looked at whether women with ME/CFS, fibromyalgia, or IBS (conditions involving central nervous system sensitivity) had worse outcomes after surgery for pelvic organ prolapse compared to women without these conditions. The researchers found that women with these central sensitivity syndromes reported more persistent symptoms, more pain, and lower satisfaction with surgery even when the surgery was technically successful.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study.

Bourke, Julius H, Wodehouse, Theresa, Clark, Lucy V et al.·Journal of psychosomatic research·2021

This study tested whether ME/CFS and fibromyalgia involve a condition called 'central sensitisation,' where the nervous system becomes overly sensitive to pain signals. Researchers compared pain sensitivity in 19 ME/CFS patients, 19 fibromyalgia patients, and 20 healthy people using physical tests. They found that 84% of ME/CFS patients and 95% of fibromyalgia patients showed signs of central sensitisation, while none of the healthy controls did.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records.

Chandan, Joht Singh, Keerthy, Deepiksana, Gokhale, Krishna Margadhamane et al.·European journal of pain (London, England)·2021

This study looked at whether women who experienced domestic abuse were more likely to develop conditions involving chronic pain and nervous system sensitivity, such as fibromyalgia and ME/CFS. Researchers compared health records of over 22,000 women who had experienced abuse with nearly 45,000 women who had not. They found that abuse survivors had significantly higher rates of several pain-related conditions, suggesting that trauma may trigger or worsen these syndromes.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

Pressure Point Thresholds and ME/CFS Comorbidity as Indicators of Patient's Response to Manual Physiotherapy in Fibromyalgia.

Falaguera-Vera, Francisco Javier, Garcia-Escudero, María, Bonastre-Férez, Javier et al.·International journal of environmental research and public health·2020

This study tested whether hands-on physiotherapy (manual therapy) could help people with fibromyalgia (FM) by reducing pain sensitivity and improving quality of life. Researchers measured pain sensitivity before and after treatment using a special device called an algometer. The main finding was that people with fibromyalgia alone responded better to the therapy than those who had both fibromyalgia and ME/CFS.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cognitive factors are associated with disability and pain, but not fatigue among physiotherapy attendees with persistent pain and fatigue.

Thompson, Dave P, Antcliff, Deborah, Woby, Steve R·Physiotherapy·2020

This study looked at how thoughts and beliefs affect pain, disability, and fatigue in people with long-term pain and exhaustion who were receiving physiotherapy. Researchers found that how confident people felt about managing their condition (self-efficacy) and how much they catastrophized (worried excessively) about their symptoms were linked to pain levels and disability, but surprisingly were not linked to fatigue levels.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia.

Surian, Amber A, Baraniuk, James N·Scientific reports·2020

This study measured how sensitive to pain women with ME/CFS, Gulf War Illness, and fibromyalgia are compared to healthy controls. Researchers used a tool called a dolorimeter to apply pressure to 18 specific body points and measured how much pressure it took before women felt pain. Women with these illnesses felt pain at much lower pressure levels than healthy women, showing they have widespread increased pain sensitivity.

Pain and SensitizationDiagnostics
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Health Conditions and Psychotic Experiences: Cross-Sectional Findings From the American Life Panel.

Oh, Hans, Smith, Lee, Koyanagi, Ai·Frontiers in psychiatry·2020

This study looked at whether people who experience psychotic symptoms (like unusual beliefs or perceptions) also tend to have more physical health problems. Researchers surveyed a representative group of American adults and found that people reporting lifetime psychotic experiences were more likely to have conditions like chronic fatigue syndrome, chronic pain, sleep disorders, migraines, and gastrointestinal problems. The more health conditions someone had, the stronger the association with psychotic experiences.

Pain and SensitizationSleep
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

OnabotulinumtoxinA Is an Effective Treatment for Chronic Migraine in Patients With Comorbid Fibromyalgia.

Sastre Real, María, Díaz de Terán, Javier·Frontiers in neurology·2020

This study looked at whether a migraine treatment called botulinum toxin (Botox) could help people who have both chronic migraines and fibromyalgia. Researchers found that about two-thirds of patients improved within 3 months, and by 12 months, nearly 70% had at least a 50% reduction in severe headache days. The treatment was generally safe with only mild side effects.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The proportion of women with central sensitivity syndrome in gynecology outpatient clinics (GOPDs).

Vij, Monika, Davies, Anthony, Dua, Anu et al.·International urogynecology journal·2019

This study looked at women visiting gynecology clinics whose symptoms didn't match what doctors could see on physical exams or tests. Researchers gave these women a questionnaire about pain sensitivity and related symptoms. They found that 37% of the women screened positive for central sensitization—a condition where the nervous system becomes more sensitive to pain and other sensations. Many of these women also had other conditions like migraine, depression, anxiety, IBS, and ME/CFS.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Physical Examination for Men and Women With Urologic Chronic Pelvic Pain Syndrome: A MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Network Study.

Yang, Claire C, Miller, Jane L, Omidpanah, Adam et al.·Urology·2018

This study looked at physical examination findings in people with chronic pelvic pain to see if doctors could identify characteristic patterns. Researchers examined 62 people with pelvic pain and compared them to 42 people with chronic fatigue syndrome and 39 healthy people. They found that people with pelvic pain were much more likely to have tender muscles in the pelvic floor area, and a special extended examination could help identify which specific areas were affected.

Pain and Sensitization
E2 ModeratePEM not requiredWeak / uncertainCross-SectionalEditor reviewed

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes.

Van Den Houte, Maaike, Van Oudenhove, Lukas, Van Diest, Ilse et al.·Frontiers in psychology·2018

This study looked at how the body's natural pain-blocking system works in people with fibromyalgia and chronic fatigue syndrome (CFS), and whether mood, depression, or heart rate variability might affect this system. Researchers compared 78 patients with these conditions to 33 healthy people using a test where they applied cold and electrical stimuli to see if pain would decrease. Unfortunately, the main pain-blocking effect the researchers expected to find did not appear in either group, so they could not draw clear conclusions about what affects pain modulation.

Pain and SensitizationAutonomic Nervous System
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Endometriosis increased the risk of bladder pain syndrome/interstitial cystitis: A population-based study.

Wu, Chia-Chang, Chung, Shiu-Dong, Lin, Herng-Ching·Neurourology and urodynamics·2018

This study found that women with endometriosis (a condition where tissue similar to the uterine lining grows outside the uterus) have a significantly higher risk of developing bladder pain syndrome/interstitial cystitis (BPS/IC), a chronic bladder pain condition. Over a 3-year period, about 4 times as many women with endometriosis developed BPS/IC compared to women without endometriosis. This suggests these two painful conditions may share common underlying mechanisms.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Activity Pacing is Associated With Better and Worse Symptoms for Patients With Long-term Conditions.

Antcliff, Deborah, Campbell, Malcolm, Woby, Steve et al.·The Clinical journal of pain·2017

This study looked at different ways people with chronic fatigue, fibromyalgia, and chronic pain manage their activities day-to-day. Researchers found that some pacing strategies work better than others: spreading activities consistently throughout the day helped, but drastically cutting back activities was linked to feeling worse. The study suggests that how you pace your activities matters—not all pacing strategies are equally helpful.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceMethods-PaperEditor reviewed

Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory.

Neblett, Randy, Hartzell, Meredith M, Mayer, Tom G et al.·Pain practice : the official journal of World Institute of Pain·2017

Researchers created and tested a scoring system called the Central Sensitization Inventory (CSI) to help doctors identify when someone's symptoms may be caused by their nervous system being overly sensitive to pain signals. The study divided CSI scores into five levels—from subclinical to extreme—and confirmed that higher scores are associated with having more chronic conditions like fibromyalgia and ME/CFS, as well as higher levels of depression, sleep problems, and disability.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Characteristics of hyperacusis in the general population.

Paulin, Johan, Andersson, Linus, Nordin, Steven·Noise & health·2016

This study looked at how common sound sensitivity (hyperacusis) is in the general population and what characteristics people with this condition share. Researchers surveyed thousands of people and found that sound sensitivity often occurs alongside other conditions like ME/CFS, anxiety, depression, and fibromyalgia. People with sound sensitivity tend to avoid loud environments and may seek medical help for their symptoms.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Specific and number of comorbidities are associated with increased levels of temporomandibular pain intensity and duration.

Dahan, Haissam, Shir, Yoram, Velly, Ana et al.·The journal of headache and pain·2015

This study examined how jaw pain (temporomandibular disorder) relates to other chronic pain conditions, particularly in people with ME/CFS. Researchers found that people with jaw pain who also had migraine or ME/CFS experienced more severe and longer-lasting jaw pain. Having multiple pain conditions at the same time was linked to worse jaw pain symptoms.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter.

Ickmans, Kelly, Meeus, Mira, De Kooning, Margot et al.·Pain physician·2015

This study looked at whether pain and thinking problems are connected in people with ME/CFS, and whether having fibromyalgia alongside ME/CFS changes this relationship. Researchers tested 48 patients with ME/CFS (some with fibromyalgia, some without) and 30 healthy people on memory and attention tasks, then measured their pain responses. They found that the type of pain problem matters: in patients with both conditions, a specific pain-processing difference predicted thinking problems, while in ME/CFS-only patients, reported pain levels predicted thinking problems.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Painful Bladder Filling and Painful Urgency are Distinct Characteristics in Men and Women with Urological Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

Lai, H Henry, Krieger, John N, Pontari, Michel A et al.·The Journal of urology·2015

This study looked at bladder pain patterns in people with chronic pelvic pain conditions. Researchers found that most patients experienced either pain when their bladder filled up or pain/pressure sensations when feeling the urge to urinate. People with these bladder symptoms also reported more severe pain, more frequent urges to urinate, depression, fatigue, and poorer quality of life compared to those without these specific bladder symptoms.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Frequency of Migraine Headaches in Patients With Fibromyalgia.

Vij, Brinder, Whipple, Mary O, Tepper, Stewart J et al.·Headache·2015

This study examined how often people with fibromyalgia experience migraine headaches. Researchers surveyed over 1,700 fibromyalgia patients and found that about 56% met the criteria for migraines. People with both conditions were more likely to also have depression, anxiety, IBS, and chronic fatigue syndrome, suggesting these overlapping conditions increase overall burden on patients.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation.

Rayhan, Rakib U, Ravindran, Murugan K, Baraniuk, James N·Frontiers in physiology·2013

This study found that migraines are very common in people with ME/CFS and Gulf War Illness—occurring in about 8 out of 10 ME/CFS patients and 6 out of 10 Gulf War Illness patients, compared to only 1 out of 8 healthy people. The researchers suggest that both conditions may affect how the brain and nervous system process pain, and that doctors should routinely check for and treat migraines in patients with these illnesses.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Latent class analysis of comorbidity patterns among women with generalized and localized vulvodynia: preliminary findings.

Nguyen, Ruby Hn, Veasley, Christin, Smolenski, Derek·Journal of pain research·2013

This study examined 1,457 women with vulvodynia (chronic vulvar pain) to understand which other pain conditions tend to occur together. Researchers found that women with more severe vulvar pain were much more likely to also have multiple other pain conditions, particularly irritable bowel syndrome and fibromyalgia. The findings suggest that these different pain conditions may share common underlying causes.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample.

Neblett, Randy, Cohen, Howard, Choi, YunHee et al.·The journal of pain·2013

This study tested a questionnaire called the Central Sensitization Inventory (CSI) to see if it could help doctors identify patients with conditions like ME/CFS, fibromyalgia, and irritable bowel syndrome. Researchers believe these conditions may share a common cause: the nervous system becoming overly sensitive to pain and other stimuli. The study found that a CSI score of 40 or higher was a good way to identify patients with these central sensitivity syndromes.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceGuidelineEditor reviewed

How to explain central sensitization to patients with 'unexplained' chronic musculoskeletal pain: practice guidelines.

Nijs, Jo, Paul van Wilgen, C, Van Oosterwijck, Jessica et al.·Manual therapy·2011

Central sensitization is a condition where the nervous system becomes overly sensitive to pain signals, making people feel pain from things that normally wouldn't hurt. This guideline explains that teaching patients about how their nervous system works—called pain physiology education—can help them understand their pain and feel better. The education works best when delivered in face-to-face sessions with written materials, and it has helped people with fibromyalgia, chronic fatigue syndrome, and other long-term pain conditions.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.

Nickel, J Curtis, Tripp, Dean A, Pontari, Michel et al.·The Journal of urology·2010

This study looked at how often bladder pain syndrome occurs alongside other conditions like irritable bowel syndrome, fibromyalgia, and ME/CFS. Researchers found that people with bladder pain syndrome were much more likely to have these other conditions compared to healthy controls. Importantly, people who had multiple overlapping conditions experienced worse pain, sleep problems, depression, and lower quality of life than those with just one condition.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Latent class analysis of functional somatic symptoms in a population-based sample of twins.

Kato, Kenji, Sullivan, Patrick F, Pedersen, Nancy L·Journal of psychosomatic research·2010

This study looked at how people with chronic fatigue and multiple physical symptoms cluster into different groups. Researchers studied over 28,000 twins and found five distinct groups: those with no symptoms, those mainly tired, those with stomach problems, those with pain, and those with many symptoms across all areas. The study suggests that while genes play a small role, environmental factors (like stress, infections, or lifestyle) are much more important in determining who develops these symptoms.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

Tietjen, Gretchen E, Brandes, Jan L, Peterlin, B Lee et al.·Headache·2010

This study looked at people with migraine who came to headache clinics and asked whether childhood trauma (abuse or neglect) was connected to having multiple pain conditions at the same time, including chronic fatigue syndrome. They found that people who experienced emotional abuse or physical neglect as children were more likely to have multiple pain conditions as adults, even after accounting for depression and anxiety.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

"Functional" or "psychosomatic" symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression.

Maes, Michael·Neuro endocrinology letters·2009

This study looked at whether depression and ME/CFS share similar physical symptoms like fatigue, muscle pain, and feeling like you have an infection. Researchers found that people with severe depression often experience these "body-centered" symptoms as a major part of their illness. The findings suggest that doctors should pay more attention to these physical symptoms when diagnosing and treating depression.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Allodynia in migraine: association with comorbid pain conditions.

Tietjen, Gretchen E, Brandes, Jan L, Peterlin, B Lee et al.·Headache·2009

This study looked at how often migraine patients experience allodynia—pain or discomfort from things that normally wouldn't hurt, like light touch on the skin. The researchers found that 60% of migraine patients had at least one allodynic symptom, and those with allodynia were much more likely to also have other chronic pain conditions like fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome, as well as depression and anxiety.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Assessment of vulvodynia symptoms in a sample of US women: a prevalence survey with a nested case control study.

Arnold, Lauren D, Bachmann, Gloria A, Rosen, Raymond et al.·American journal of obstetrics and gynecology·2007

This study looked at how common vulvodynia (chronic pain in the vulva) is among American women and found that about 4% currently experience it. Women with vulvodynia were more likely to also have other conditions like chronic fatigue syndrome, fibromyalgia, depression, and irritable bowel syndrome. Many women reported that the pain significantly affected their sexual life and daily activities.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Endometriosis is associated with prevalence of comorbid conditions in migraine.

Tietjen, Gretchen E, Bushnell, Cheryl D, Herial, Nabeel A et al.·Headache·2007

This study found that women with migraines who also have endometriosis (a painful condition affecting the uterus) experience more frequent and severe headaches than women with migraines alone. Women with both conditions were also more likely to have other related conditions like chronic fatigue syndrome, anxiety, and bladder pain. The findings suggest these conditions may share common underlying factors, possibly related to hormones.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

A case-control study of risk factors for arm pain presenting to primary care services.

Ryall, Claire, Coggon, David, Peveler, Robert et al.·Occupational medicine (Oxford, England)·2006

This study looked at why some people develop arm pain and sought medical help for it. Researchers compared 132 people with arm pain to 127 people without arm pain and found that anxiety, depression, health worry, and having other conditions like chronic fatigue syndrome were all strongly linked to arm pain. Some physical activities like repetitive wrist movements and carrying heavy items were also associated with arm pain, especially when there was a specific diagnosis.

Pain and Sensitization
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Ambulatory monitoring of physical activity and symptoms in fibromyalgia and chronic fatigue syndrome.

Kop, Willem J, Lyden, Angela, Berlin, Ali A et al.·Arthritis and rheumatism·2005

This study used activity trackers to measure how much people with ME/CFS and fibromyalgia move during daily life, and whether their pain and fatigue change based on activity levels. The researchers found that patients with these conditions did less intense activity and experienced more pain and fatigue when they were less active, but interestingly, having pain or fatigue seemed to cause them to reduce activity rather than the other way around.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Health and functional status of twins with chronic regional and widespread pain.

Aaron, Leslie A, Arguelles, Lester M, Ashton, Suzanne et al.·The Journal of rheumatology·2002

This study looked at twins where one had chronic pain (either in one area or widespread) and the other did not, to understand how pain affects health and function independent of ME/CFS. Researchers found that chronic pain significantly worsens general health perception, physical functioning, and sleep quality, effects that remain even after accounting for ME/CFS. However, the mental health impact of pain appears closely linked to having ME/CFS symptoms together.

Pain and SensitizationSleep
E2 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness.

Bourdette, D N, McCauley, L A, Barkhuizen, A et al.·Journal of occupational and environmental medicine·2001

Researchers surveyed over 2,000 Gulf War veterans and conducted detailed medical exams on 443 of them to look for unexplained health symptoms. They found that many veterans experienced overlapping symptoms—including cognitive problems, fatigue, and muscle pain—that resembled conditions like fibromyalgia and chronic fatigue syndrome, but they found few clear physical differences between sick and healthy veterans.

Pain and SensitizationCognitive Impairment
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.

Aaron, L A, Burke, M M, Buchwald, D·Archives of internal medicine·2000

This study found that ME/CFS, fibromyalgia, and temporomandibular disorder (TMD) often occur together in the same patients and share similar symptoms like pain, fatigue, and sleep problems. The researchers also discovered that patients with these conditions frequently experience other illnesses like irritable bowel syndrome and headaches—much more often than healthy people do. The study suggests these conditions may be connected in some way we don't yet fully understand.

Pain and SensitizationSleepCognitive Impairment
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Prevalence of chronic fatigue and chemical sensitivities in Gulf Registry Veterans.

Kipen, H M, Hallman, W, Kang, H et al.·Archives of environmental health·1999

This study looked at symptoms reported by Gulf War veterans to see how many experienced chronic fatigue and chemical sensitivities. Researchers found that about 16% of veterans met the standard criteria for ME/CFS, about 13% had multiple chemical sensitivities, and a small percentage had both conditions. The findings suggest these conditions were common among Gulf War veterans, though the study was based only on questionnaire responses rather than medical exams.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

The relationship between fibromyalgia and interstitial cystitis.

Clauw, D J, Schmidt, M, Radulovic, D et al.·Journal of psychiatric research·1997

This study compared symptom patterns in people with fibromyalgia, interstitial cystitis (a bladder pain condition), and healthy people. Researchers found that fibromyalgia and IC patients reported very similar types of symptoms beyond their primary complaints, and both groups showed increased pain sensitivity throughout their bodies—not just in the areas they typically experienced pain.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents.

Bell, D S, Bell, K M, Cheney, P R·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study looked at whether children diagnosed with chronic fatigue syndrome (CFS) also had fibromyalgia, a condition involving widespread muscle pain and tender points. Researchers found that about 30% of children with CFS met the criteria for fibromyalgia, and these children experienced more muscle pain, sleep problems, and neurological symptoms than those without fibromyalgia. The study suggests that CFS and fibromyalgia in children may be closely related or even the same condition.

Pain and SensitizationSleep
E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice.

Goldenberg, D L, Simms, R W, Geiger, A et al.·Arthritis and rheumatism·1990

This study looked at whether people with chronic fatigue also have fibromyalgia, a condition involving widespread muscle pain and tender points. Researchers examined 27 patients with debilitating fatigue lasting at least 6 months and found that 70% of them had the widespread pain and tender points typical of fibromyalgia. This suggests that many people with chronic fatigue may also have fibromyalgia.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Pain in adolescent chronic fatigue following Epstein-Barr virus infection.

Brodwall, Elias Myrstad, Pedersen, Maria, Asprusten, Tarjei Tørre et al.·Scandinavian journal of pain·2020

This study looked at pain symptoms in teenagers who developed chronic fatigue after a common virus infection (Epstein-Barr virus). Researchers compared teenagers who had the virus and became fatigued, those who had the virus but did not become fatigued, and healthy teenagers without the virus. They found that the fatigued group reported significantly more pain symptoms and that the amount of pain they experienced was strongly linked to their quality of life.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study.

Moldofsky, Harvey, Patcai, John·BMC neurology·2011

This study looked at people who had severe SARS infection and were unable to return to work for over a year afterward. These patients experienced long-lasting fatigue, widespread muscle pain, weakness, depression, and poor sleep quality. Researchers found that their sleep patterns and symptoms were very similar to those seen in fibromyalgia and chronic fatigue syndrome.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Prevalence of Bodily Distress Syndrome and Prediction of Patient Outcomes: Cohort Study of 3762 Individuals With Persistent Pain.

Landmark, Live, Sunde, Hans Fredrik, Fors, Egil A et al.·European journal of pain (London, England)·2026

This study looked at how multiple physical symptoms often occur together in people with chronic pain, using a framework called Bodily Distress Syndrome (BDS). Among 3,762 people attending a specialized pain clinic, 92.5% showed moderate to severe BDS, and those with BDS experienced more severe symptoms and psychological stress. After one year, people with BDS improved less and reported less benefit from treatment compared to those without BDS.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Clinical Importance of Central Sensitization and Neuropathic Pain in The Treatment and Follow-Up of Patients with Psoriasis and Psoriatic Arthritis.

Koca, Tuba Tülay, Göğebakan, Hasan, Nazik, Hülya et al.·Indian journal of dermatology·2026

This study looked at whether people with skin and joint conditions (psoriasis and psoriatic arthritis) experience unusual pain processing in their nervous system, similar to what happens in conditions like fibromyalgia. Researchers found that many patients with these conditions had signs of nervous system sensitization and neuropathic pain (nerve-related pain). The more active their disease was, the more likely they were to have these pain processing problems.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Adverse effects of obesity on overall health, quality of life, and related physical health metrics: A cross-sectional and longitudinal study from the All of Us Research Program.

Yao, Zhiqi, Tchang, Beverly G, Chae, Kacey et al.·Journal of internal medicine·2025

This study looked at over 323,000 people in the United States to understand how obesity affects overall health and quality of life. Researchers found that people with higher body weight reported worse health, more pain, more fatigue, and greater difficulty with physical activity compared to people of normal weight. The effects were strongest in people with the most severe obesity, who were nearly 4 times more likely to report poor health and severe pain.

Pain and SensitizationSleep
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Effect of Central Sensitization in Patients with Familial Mediterranean Fever, Axial Spondyloarthritis, and Both Diseases.

Kaya, Mehmet Nur, Kılıç, Özlem, Doğan, Abdullah et al.·Cureus·2023

This study looked at whether three groups of patients—those with familial Mediterranean fever (FMF), a type of spinal arthritis (axSpA), or both conditions—experience heightened pain sensitivity and related symptoms like fatigue and fibromyalgia compared to healthy people. Researchers used a questionnaire to measure 'central sensitization,' which is when the nervous system amplifies pain signals. They found that patients with these conditions did score higher on pain sensitivity measures than healthy controls, and chronic fatigue was particularly common in the FMF group.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

The Impact of Micro RNA-320a Serum Level on Severity of Symptoms and Cerebral Processing of Pain in Patients with Fibromyalgia.

Hussein, Mona, Fathy, Wael, Abdelaleem, Enas A et al.·Pain medicine (Malden, Mass.)·2022

Researchers measured a molecule called miR-320a in the blood of people with fibromyalgia and compared it to healthy people. They found that fibromyalgia patients had higher levels of this molecule, and those with higher levels tended to have worse symptoms like pain, fatigue, sleep problems, and depression. However, this molecule did not appear to affect how the brain processes pain signals.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceRegistry-ResourceEditor reviewed

Sarcoidosis among US Hispanics in a Nationwide Registry.

Innabi, Ayoub, Alzghoul, Bashar N, Kalra, Saminder et al.·Respiratory medicine·2021

This study looked at how sarcoidosis (a disease that causes inflammation in the body) affects Hispanic patients in the United States compared to non-Hispanic patients. Researchers surveyed nearly 3,835 people and found that Hispanic patients with sarcoidosis experience more depression, chronic pain, sleep problems, and job loss than non-Hispanic patients. The findings suggest that doctors may need to approach treatment differently for Hispanic patients with this condition.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Processing of Laser-Evoked Potentials in Patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and Healthy Controls: A Case-Control Study.

Goudman, Lisa, Daenen, Liesbeth, Mouraux, Andre et al.·Pain medicine (Malden, Mass.)·2020

Researchers used a specialized brain test called laser-evoked potentials (LEPs) to measure how the nervous system responds to heat pain in ME/CFS patients, whiplash patients, and healthy people. The test involved brief laser pulses applied to the hand and foot while recording brain activity. The study found that ME/CFS patients' nervous systems responded to pain in basically the same way as healthy people, which suggests their pain-sensing pathways are working normally.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Musculoskeletal Pain in Individuals With Inflammatory Bowel Disease Reflects Three Distinct Profiles.

Falling, Carrie, Stebbings, Simon, Baxter, George D et al.·The Clinical journal of pain·2019

Most people with inflammatory bowel disease (IBD) experience muscle and joint pain, but the pain works differently in different people. This study found three distinct groups: one with mixed types of pain, one with pain driven by nervous system sensitivity, and one with pain in specific areas that improves when the IBD is under control. The group with nervous system-driven pain had higher rates of depression, anxiety, and chronic fatigue syndrome.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study.

Collin, Simon M, Nijs, Jo, Meeus, Mira et al.·Pain physician·2017

This study tested how people with ME/CFS, people with multiple sclerosis (MS), and healthy people respond to pain. Researchers found that people with ME/CFS have lower pain thresholds and more pain amplification than people with MS, suggesting their nervous systems may process pain differently. These findings suggest that ME/CFS pain may involve a different biological mechanism than MS pain.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Occupational exposure and health problems among Polish denturists: a population-based study in Łódź province.

Garus-Pakowska, Anna, Leśniewska, Agnieszka, Gaszyńska, Ewelina et al.·International dental journal·2016

This study surveyed 103 denturists (dental laboratory workers) in Poland to understand how their work affects their health. The researchers found that over 60% experienced chronic fatigue syndrome and 70% had back pain, along with skin irritation and eye problems. Poor workplace design and stress from work organization were identified as major contributing factors.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

Keller, Joseph, Chen, Yi-Kuang, Lin, Herng-Ching·International urogynecology journal·2013

This study looked at whether people with bladder pain syndrome/interstitial cystitis (BPS/IC) are more likely to have had kidney stones or other urinary stones. Researchers compared about 9,000 people newly diagnosed with BPS/IC to over 46,000 similar people without BPS/IC and found that those with BPS/IC were significantly more likely to have a history of urinary stones, particularly bladder stones.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

A prospective genetic marker of the visual-perception disorder Meares-Irlen syndrome.

Loew, Stephen J, Watson, Kenneth·Perceptual and motor skills·2012

This study looked at whether a specific gene called APOB might be linked to Meares-Irlen syndrome, a condition that affects how the eyes process visual information and can make reading difficult. The researchers found that certain variations of this gene were more common in people with Meares-Irlen syndrome than in people without it. This is interesting because the same gene has been connected to problems with fat and cholesterol metabolism, which have also been found in ME/CFS and other conditions.

Pain and Sensitization
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Clinical characteristics of patients with medically unexplained chronic widespread pain: a primary care center study.

Lee, Kye Hwa, Kim, Cheol Hwan, Shin, Ho Cheol et al.·Korean journal of family medicine·2011

This study examined 109 patients with chronic widespread pain to understand what makes medically unexplained pain different from pain caused by known medical or psychological conditions. Researchers found that patients with unexplained pain had more tender points on their body, greater fatigue, and more functional impairment than those with pain linked to known medical causes, but were very similar to those with pain linked to psychological factors.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Physical and psychosocial correlates of severe fatigue in rheumatoid arthritis.

van Hoogmoed, Dewy, Fransen, Jaap, Bleijenberg, Gijs et al.·Rheumatology (Oxford, England)·2010

This study looked at severe fatigue in people with rheumatoid arthritis (RA), a condition that causes joint inflammation. Researchers found that 42% of RA patients experienced severe fatigue that felt frustrating and exhausting. Importantly, this severe fatigue was more closely linked to pain, mood, sleep quality, and how patients thought about their fatigue—rather than to inflammation markers alone.

Pain and SensitizationSleep
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Co-occurrence and associations of pain and fatigue in a community sample of Dutch adults.

Creavin, Samuel T, Dunn, Kate M, Mallen, Christian D et al.·European journal of pain (London, England)·2010

This study looked at how often pain and fatigue occur together in everyday people. Researchers found that when someone has chronic widespread pain, they are much more likely to also experience persistent fatigue, and vice versa. People who had both symptoms were more likely to also experience anxiety or depression, and certain factors like being overweight, having other chronic diseases, or low activity levels made having both symptoms more common.

Pain and Sensitization
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Odor perception: multiple chemical sensitivities, chronic fatigue, and asthma.

Caccappolo, E, Kipen, H, Kelly-McNeil, K et al.·Journal of occupational and environmental medicine·2000

This study tested whether people with chemical sensitivities, chronic fatigue, and asthma have unusually sensitive noses. Researchers measured how well different groups could smell odors and identify them. While people with chemical sensitivities didn't actually detect odors at lower levels than others, they did report feeling more physical symptoms and found certain smells more unpleasant than other groups did.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Myopraktikk (NO): A Narrative Review and Conceptual Hypothesis on Intrafasciomembranal Fluid Pressure, Biotensegrity, and Immediate Remote Myofascial Responses.

Hopen, Stig Runar, Mjøen, Tor Arne·Cureus·2025

This article proposes a new theory about muscle pain and stiffness called Myopraktikk, which focuses on fluid pressure building up in the spaces around muscles. The authors suggest that when fluid pressure increases in these areas, it can cause muscles to feel tight, knotted, and painful—similar to what happens in conditions like ME/CFS and fibromyalgia. According to their hypothesis, releasing this pressure through manual treatment may help reduce symptoms in both the treated area and elsewhere in the body.

Pain and Sensitization
E3 PreliminaryPEM unclearModerate confidenceLongitudinalEditor reviewed

Disentangling pain and fatigue in chronic fatigue syndrome: a resting state connectivity study before and after cognitive behavioral therapy.

van der Schaaf, Marieke E, Geerligs, Linda, Toni, Ivan et al.·Psychological medicine·2024

This study looked at how fatigue and pain affect different networks in the brain of ME/CFS patients by taking brain scans at rest. The researchers found that fatigue and pain involve different brain circuits, suggesting they may be caused by different mechanisms. After cognitive behavioral therapy (CBT), patients who improved showed better communication between brain regions associated with movement and the brain's resting network.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial.

Oka, Takakazu, Yamada, Yu, Lkhagvasuren, Battuvshin et al.·BioPsychoSocial medicine·2022

Researchers tested whether wasabi extract—specifically a compound called 6-MSITC that has anti-inflammatory properties—could help people with ME/CFS. Fifteen patients took the supplement daily for 12 weeks, and many reported improvements in headaches, muscle pain, brain fog, and cognitive problems like word-finding difficulties. The study found measurable improvements in pain sensitivity and thinking speed, though overall fatigue scores did not change significantly.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM unclearModerate confidenceCross-SectionalEditor reviewed

Experiences of pain in paediatric chronic fatigue syndrome/myalgic encephalomyelitis: a single-centre qualitative study.

Serafimova, Teona, Ascough, Caitlin, Parslow, Roxanne Morin et al.·BMJ paediatrics open·2022

This study explored how children with ME/CFS experience pain by interviewing 13 young people (average age 15). Researchers found that pain is very common, highly varied, and significantly impacts daily life—affecting physical activity, eating, schooling, and mental health. Most importantly, the children reported that current treatments don't work well, highlighting an urgent need for better pain management options.

Pain and Sensitization
E3 PreliminaryPEM unclearModerate confidenceCross-SectionalEditor reviewed

Orthostatic stress testing in myalgic encephalomyelitis/chronic fatigue syndrome patients with or without concomitant fibromyalgia: effects on pressure pain thresholds and temporal summation.

van Campen, C Linda M C, Rowe, Peter C, Verheugt, Freek W A et al.·Clinical and experimental rheumatology·2021

This study tested how standing up quickly (which can trigger ME/CFS symptoms) affects pain sensitivity in ME/CFS patients. Researchers measured how much pressure patients could tolerate on their finger and shoulder before and after a tilt test. They found that ME/CFS patients became more pain-sensitive after the tilt test, meaning their bodies responded to pain more strongly than healthy people, and this effect was even more pronounced in those who also had fibromyalgia.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Chronic Fatigue Syndrome and chronic pain conditions - vitally protective systems gone wrong.

Pedersen, Maria·Scandinavian journal of pain·2019

This review explains that ME/CFS and chronic pain conditions share important similarities—both involve protective body signals that were helpful in the short term but become problematic when they persist long-term. The authors suggest that our brain's tendency to anticipate and predict threats may play a role in keeping these conditions going, which helps explain why treatments focusing on stress relief and changing thought patterns can sometimes help patients improve.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Anaesthesia for patients with idiopathic environmental intolerance and chronic fatigue syndrome.

Fisher, M McD, Rose, M·British journal of anaesthesia·2008

This study looked at how anesthesia should be safely given to ME/CFS patients undergoing surgery. Researchers found that while some patients experienced side effects after anesthesia, these were not severe allergic reactions and were usually temporary. The study suggests that doctors can use standard anesthesia techniques for ME/CFS patients, simply avoiding any drugs the patient has previously reacted badly to.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

[Fibromyalgia and chronic fatigue syndrome in children and adolescents].

Galanopoulos, Ng, Kampakis, Gp, Ladopoulou, Kf·Psychiatrike = Psychiatriki·2007

This review discusses fibromyalgia and chronic fatigue syndrome (ME/CFS) in children and teenagers, noting that both conditions are fairly common in this age group. Patients with these conditions experience widespread muscle pain, exhaustion, depression, headaches, and sleep problems that can significantly impact school, family life, and overall development. The authors emphasize that early diagnosis and treatment combining medication, physical therapy, and psychological support are important for helping young people manage these conditions.

Pain and SensitizationSleep
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

[Clinical features of chronic fatigue syndrome--symptoms].

Ban, Nobutaro, Saiki, Takuya, Ko, Gyoshin et al.·Nihon rinsho. Japanese journal of clinical medicine·2007

This review article summarizes the most common symptoms experienced by people with ME/CFS. The researchers identified and described the top 10 symptoms in detail, including severe fatigue, problems with memory and concentration, muscle pain, poor sleep, and headaches. Understanding these symptom patterns can help doctors recognize and diagnose ME/CFS more accurately.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryCase-ControlEditor reviewed

Efficacy of neurotropin in chronic fatigue syndrome: a case report.

Toda, Katsuhiro, Kimura, Hiroaki·Hiroshima journal of medical sciences·2006

This case report describes one 28-year-old man with ME/CFS who was treated with a medication called Neurotropin (four tablets daily). His fatigue and widespread pain began improving within a week, and his sleep, focus, and memory improved within two weeks. He stopped taking the medication after 11 weeks and remained symptom-free for at least 5 months afterward.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

[Multiple chemical sensitivity in sick-building syndrome].

Arnold Llamosas, Pablo A, Arrizabalaga Clemente, Pilar, Bonet Agusti, Montserrat et al.·Medicina clinica·2006

This study describes a dialysis worker who developed severe chronic fatigue and chemical sensitivities after prolonged exposure to poor indoor air quality in a poorly ventilated building. The person experienced eye irritation, breathing problems, and other symptoms that improved when the environmental conditions were examined and their connection to the illness was confirmed. The case highlights that healthcare facilities can expose workers to unhealthy air and chemical environments that may trigger ME/CFS-like illnesses.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Qi therapy (external qigong) for chronic fatigue syndrome: case studies.

Shin, Yong-Il, Lee, Myeong Soo·The American journal of Chinese medicine·2005

This study looked at whether Qi therapy (a hands-on energy-based technique from traditional Chinese medicine) might help people with ME/CFS feel better. Two patients who received Qi therapy reported feeling more mentally relaxed and found it easier to cope with their pain and tiredness. While these are only two cases and more research is needed, the results suggest Qi therapy might be worth studying further as a complementary approach.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

The effects of repeated thermal therapy for two patients with chronic fatigue syndrome.

Masuda, Akinori, Kihara, Takashi, Fukudome, Tsuyoshi et al.·Journal of psychosomatic research·2005

This study followed two ME/CFS patients who tried a type of heat therapy called far-infrared sauna (heated to 60°C) combined with warming afterward. After about 15-25 sessions, both patients reported major improvements in fatigue, pain, sleep problems, and fever. They continued the therapy once or twice a week for a year and did not get worse, even after stopping their previous medication.

Pain and SensitizationSleep
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

[Chronic fatigue syndrome and multiple chemical hypersensitivity after insecticide exposure].

Fernández-Solà, Joaquim, Lluís Padierna, Meritxell, Nogué Xarau, Santiago et al.·Medicina clinica·2005

This study followed 26 people who developed ME/CFS after being exposed to insecticide sprays at their workplace. Most patients were women who first experienced airway inflammation and digestive problems, followed by brain fog, muscle pain, and fatigue. About one-third also developed chemical sensitivity. The researchers emphasize that proper ventilation and safety precautions during and after insecticide use are crucial to prevent these illnesses.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Physiology and pathophysiology of the 5-HT3 receptor.

Färber, L, Haus, U, Späth, M et al.·Scandinavian journal of rheumatology. Supplement·2004

This review examines how a specific brain chemical receptor called 5-HT3 works in the body and what happens when it malfunctions. The researchers found that blocking this receptor with certain medications may help treat several conditions, including ME/CFS, by reducing symptoms like nausea, pain, and anxiety. However, scientists still don't fully understand exactly how this receptor causes problems in these different illnesses.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Subjective health complaints, sensitization, and sustained cognitive activation (stress).

Eriksen, H R, Ursin, H·Journal of psychosomatic research·2004

This review suggests that common symptoms like pain, tiredness, sleep problems, and digestive issues in conditions like ME/CFS may occur when the body's normal sensing system becomes overly sensitive. Rather than being caused by hidden disease, these symptoms may develop when people experience sustained stress and feel helpless, causing the nervous system to amplify normal bodily signals until they become unbearable.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryEditorialEditor reviewed

Toxicant-induced loss of tolerance.

Miller, C S·Addiction (Abingdon, England)·2001

This paper proposes a new theory called TILT (toxicant-induced loss of tolerance) that suggests the body can lose its ability to tolerate certain exposures—whether drugs or environmental chemicals—in similar ways. The author argues that both addiction and chemical sensitivity involve the same underlying breakdown in how the body normally handles these substances, which could help explain ME/CFS, fibromyalgia, and other chronic illnesses.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryEditorialEditor reviewed

Fibromyalgia and chronic fatigue syndrome: an update for athletic trainers.

Cramer, C R·Journal of athletic training·1998

This article reviews what we know about ME/CFS and fibromyalgia, two conditions that cause severe fatigue, muscle pain, and sleep problems. The authors looked at medical research and government health information to summarize how these conditions affect people, especially athletes. They discuss various treatments being tested, including exercise, relaxation therapy, and medications, and emphasize the importance of careful medical evaluation and psychological support during diagnosis and treatment.

Pain and SensitizationSleep
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

Bell, I R, Baldwin, C M, Schwartz, G E·The American journal of medicine·1998

Some people with ME/CFS and fibromyalgia react strongly to small amounts of everyday chemicals (like fragrances or pesticides) that don't normally harm others. This paper reviews evidence suggesting that the brain's limbic system—which controls emotions and basic body functions—may become overly sensitive to these chemicals, creating a chain reaction that affects multiple body systems. The authors propose that certain people are born with or develop a heightened sensitivity to this kind of stimulation, which could explain why some ME/CFS patients feel sick from exposure to low levels of chemicals.

Endocrine DisruptionPain and Sensitization
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

[Chronic fatigue syndrome. Definition, diagnostic measures and therapeutic possibilities].

Lieb, K, Dammann, G, Berger, M et al.·Der Nervenarzt·1996

ME/CFS is a disorder that causes persistent tiredness, but doctors cannot diagnose it with a simple blood test or scan. Instead, doctors use specific clinical criteria to identify the condition, while carefully ruling out other illnesses like depression or sleep problems that can look similar. Currently, there is no cure for ME/CFS, so treatment focuses on managing individual symptoms like poor sleep, pain, and mood changes with a combination of medical care and psychological support.

Pain and SensitizationSleepDiagnostics
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome.

Vecchiet, L, Montanari, G, Pizzigallo, E et al.·Neuroscience letters·1996

This study tested whether people with ME/CFS have increased pain sensitivity in their muscles compared to their skin. Researchers found that muscles were significantly more sensitive to pain in ME/CFS patients, while skin sensitivity was normal. They also discovered abnormal structures and damage in muscle cells from ME/CFS patients, including problems with mitochondria (the energy-producing parts of cells) and signs of degeneration.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

The ocular signs and symptoms of chronic fatigue syndrome.

Caffery, B E, Josephson, J E, Samek, M J·Journal of the American Optometric Association·1994

This study looked at eye problems in 25 people with ME/CFS and found that all of them experienced some eye-related symptoms. The most common issues were problems with tears and the eye's surface, as well as difficulty focusing on close objects. Eye doctors should be aware of these issues when examining ME/CFS patients.

Pain and Sensitization
E3 PreliminaryPEM unclearWeak / uncertainEditorialEditor reviewed

Pain syndromes, disability, and chronic disease in childhood.

Malleson, P N·Current opinion in rheumatology·1991

This editorial discusses how chronic pain and long-term illnesses affect children, and suggests that conditions like fibromyalgia and chronic fatigue syndrome (ME/CFS) may be related to each other. The author notes that doctors need better training to understand these complex conditions and that psychological factors may play a role in how these illnesses develop and affect children's lives.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Current understanding of nociplastic pain.

Yoo, Yeong-Min, Kim, Kyung-Hoon·The Korean journal of pain·2024

This article explains 'nociplastic pain'—a type of chronic pain that occurs when the nervous system becomes overly sensitive to pain signals, even when there is no obvious tissue damage or nerve injury. People with ME/CFS, fibromyalgia, and similar conditions often experience this kind of pain. The article describes how doctors can recognize nociplastic pain and groups it with other conditions that share this same underlying mechanism of nervous system sensitivity.

Pain and Sensitization
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

Exploring the scope of homoeopathy in combating the unfortunate consequences of post-COVID-19 survivors based on non-COVID conditions: a narrative review.

Dixit, Ashish Kumar, Giri, Nibha, Singh, Shishir·Journal of complementary & integrative medicine·2023

This review looked at whether homeopathy—a complementary medicine approach—might help people recover from long-term symptoms after COVID-19. The authors searched published research and found that homeopathy has shown some promise in treating anxiety, depression, pain, and heart problems in other conditions, and they suggest it might be worth studying for post-COVID recovery.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Possible Application of Melatonin in Long COVID.

Cardinali, Daniel P, Brown, Gregory M, Pandi-Perumal, Seithikurippu R·Biomolecules·2022

This review examines whether melatonin, a natural hormone that regulates sleep, might help people with long COVID who experience symptoms similar to ME/CFS—such as brain fog, fatigue, and muscle pain. Melatonin has several properties that could potentially help: it reduces inflammation, fights harmful molecules in the body, supports immune function, and protects nerve cells. The authors suggest melatonin might be worth studying further as a treatment for the lingering cognitive and pain symptoms some long COVID patients experience.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

[Endometriosis and chronic overlapping pain conditions].

Häuser, Winfried·Schmerz (Berlin, Germany)·2021

This review examines how endometriosis (a painful condition affecting the reproductive system) often occurs alongside other chronic pain conditions like fibromyalgia, ME/CFS, migraines, and others. The authors explain that these conditions share common underlying causes—such as childhood stress or trauma—and similar ways the nervous system processes pain signals. They recommend that doctors screen endometriosis patients for these overlapping conditions and use medications like amitriptyline or duloxetine combined with physical therapy and psychological support, rather than repeated surgeries.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue.

Teitelbaum, Jacob, Goudie, Sarah·Pharmaceuticals (Basel, Switzerland)·2021

This study tested a special form of red ginseng called HRG80 in people with ME/CFS, fibromyalgia, and post-COVID fatigue. Over one month, 188 patients took daily ginseng supplements and reported their symptoms. About 60% of participants felt better, with improvements in energy, mental clarity, sleep, and stamina.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?

Karsan, Nazia, Goadsby, Peter J·Frontiers in human neuroscience·2021

This review examines why migraine sufferers often experience fatigue, mood changes, and cognitive difficulties—symptoms that can occur hours or days before a headache arrives. Rather than being separate diseases, the authors suggest these symptoms may stem from shared brain chemistry problems in people with migraines, similar to what happens in ME/CFS and depression. The study proposes that migraine is fundamentally a disorder of how the brain processes sensory information, not just a headache condition.

Pain and Sensitization
E3 PreliminaryPEM unclearModerate confidenceCross-SectionalEditor reviewed

DNA Methylation and Brain-Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia.

Polli, Andrea, Ghosh, Manosij, Bakusic, Jelena et al.·Arthritis & rheumatology (Hoboken, N.J.)·2020

This study found that people with ME/CFS and fibromyalgia have unusual patterns in how their genes are regulated, specifically involving a molecule called BDNF that affects pain and nerve function. Researchers measured genetic markers and protein levels in blood samples and found that changes in how BDNF genes are 'switched on and off' may explain why patients experience severe fatigue, pain, and widespread body aches.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens.

Paredes, Stephania, Cantillo, Santiago, Candido, Kenneth D et al.·International journal of molecular sciences·2019

This review article explains how a brain chemical called serotonin affects pain perception, and how female hormones (estrogens) can influence serotonin levels. The authors examine the connection between serotonin, hormones, and several pain conditions including irritable bowel syndrome, fibromyalgia, and migraines. They suggest that targeting serotonin and hormone pathways might offer new treatment options for pain in the future.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology.

Hulens, Mieke, Rasschaert, Ricky, Vansant, Greet et al.·Journal of pain research·2018

This review paper proposes that ME/CFS, fibromyalgia, and a condition called idiopathic intracranial hypertension (IICH—where pressure builds up around the brain) may share similar underlying causes. All three conditions cause widespread pain, fatigue, cognitive problems, and other symptoms that could potentially be explained by increased pressure in the fluid surrounding the brain and spinal cord.

Pain and SensitizationCognitive Impairment
E3 PreliminaryPEM not requiredPreliminaryMethods-PaperEditor reviewed

Clinical Criteria of Central Sensitization in Chronic Pelvic and Perineal Pain (Convergences PP Criteria): Elaboration of a Clinical Evaluation Tool Based on Formal Expert Consensus.

Levesque, Amélie, Riant, Thibault, Ploteau, Stéphane et al.·Pain medicine (Malden, Mass.)·2018

This study created a simple checklist to help doctors identify when chronic pelvic pain is caused by the nervous system becoming overly sensitive, rather than from a structural injury or disease they can see on tests. Experts agreed on 10 key signs to look for, including pain that changes in intensity, pain triggered by normal activities, and having other conditions like fibromyalgia or chronic fatigue syndrome alongside pelvic pain.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

HPV vaccination syndrome: A clinical mirage, or a new tragic fibromyalgia model.

Martínez-Lavín, Manuel·Reumatologia clinica·2018

Some people have reported developing chronic pain and autonomic symptoms (problems with heart rate, blood pressure, and sweating) after receiving the HPV vaccine. This article reviews whether this connection is real and suggests that if it exists, these cases might share similarities with fibromyalgia—a condition involving widespread pain and nervous system dysfunction. The authors propose that understanding fibromyalgia's mechanisms could help diagnose and treat patients who develop symptoms after HPV vaccination.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Frontline Temporomandibular Joint/Orofacial Pain Therapy for Every Dental Practice.

Germain, Lisa, Malcmacher, Louis·Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995)·2017

This article explains how dentists can help patients with temporomandibular joint (jaw joint) and orofacial pain using straightforward, conservative treatment approaches. The authors note that jaw pain often occurs alongside other pain conditions, including chronic fatigue syndrome (ME/CFS), and suggest that dentists with proper training can be a first line of care for these patients.

Pain and Sensitization
E3 PreliminaryPEM not requiredModerate confidenceMethods-PaperEditor reviewed

Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli.

Dixon, Eric A, Benham, Grant, Sturgeon, John A et al.·Journal of behavioral medicine·2016

Researchers created a new questionnaire called the Sensory Hypersensitivity Scale (SHS) to measure how sensitive people are to everyday sensations like touch, sound, taste, and temperature. The tool was tested on over 1,200 people and worked well at identifying those with heightened sensory sensitivity. People with fibromyalgia scored higher on the scale than those with other types of chronic pain, suggesting the tool could help identify central sensitization—a condition where the nervous system amplifies pain signals.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

HPV vaccination syndrome. A questionnaire-based study.

Martínez-Lavín, Manuel, Martínez-Martínez, Laura-Aline, Reyes-Loyola, Paola·Clinical rheumatology·2015

This study looked at people who developed long-lasting pain, fatigue, and heart/blood pressure problems shortly after receiving the HPV vaccine. Researchers used three validated questionnaires to assess 45 people from 13 countries. Most reported muscle pain, tiredness, and dizziness, and after an average of 4 years, 93% still had severe symptoms preventing them from working or going to school.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

[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 PreliminaryPEM unclearWeak / uncertainReview-NarrativeEditor reviewed

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
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Comorbid somatic symptoms and functional status in patients with fibromyalgia and chronic fatigue syndrome: sensory amplification as a common mechanism.

Geisser, Michael E, Strader Donnell, Cathy, Petzke, Frank et al.·Psychosomatics·2008

This study looked at why people with fibromyalgia and ME/CFS experience so many body symptoms. Researchers found that both conditions may share a common problem: the nervous system amplifies sensory signals, making pain and other sensations feel stronger than they might to other people. This heightened sensitivity to stimulation appears to be a key reason why these conditions affect daily functioning, and this mechanism seems separate from depression.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome.

Meeus, Mira, Nijs, Jo·Clinical rheumatology·2007

Many people with ME/CFS experience widespread pain in addition to fatigue, similar to fibromyalgia. This paper proposes that both conditions may be caused by 'central sensitization'—a problem where the nervous system becomes overly sensitive to pain signals. The authors review evidence suggesting this mechanism could explain ME/CFS pain, though more research is needed to confirm it.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Violence, stress, and somatic syndromes.

Crofford, Leslie J·Trauma, violence & abuse·2007

This review article examines how experiences of violence and stress may trigger or worsen conditions like ME/CFS, fibromyalgia, and irritable bowel syndrome—illnesses that involve pain, exhaustion, mood changes, memory problems, and sleep issues. The authors explain that stress affects the brain and body's hormone and nervous system function, which may make people more vulnerable to developing these conditions. Understanding this connection could help us recognize how violence exposure affects long-term health.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredModerate confidenceCross-SectionalEditor reviewed

The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome.

Geisser, Michael E, Gracely, Richard H, Giesecke, Thorsten et al.·European journal of pain (London, England)·2007

Researchers tested whether laboratory pain tests (using heat and pressure) could predict the pain people with fibromyalgia and ME/CFS experience in daily life. They found that pressure-based tests were better predictors of real-world pain than heat tests, suggesting that pressure stimulation may be a more useful research tool for studying pain in these conditions.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Cranial electrotherapy stimulation and fibromyalgia.

Gilula, Marshall F·Expert review of medical devices·2007

This review examines cranial electrotherapy stimulation (CES), a treatment that uses mild electrical stimulation applied to the head to help manage fibromyalgia pain and related symptoms. While CES is not a cure-all, research suggests it may help some fibromyalgia patients feel better. The review also discusses how fibromyalgia often occurs alongside other conditions like anxiety, depression, sleep problems, and fatigue—symptoms that overlap with ME/CFS.

Pain and SensitizationSleep
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes.

Yunus, Muhammad B·Seminars in arthritis and rheumatism·2007

This paper proposes that fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, and certain headaches may all share a common underlying problem: the nervous system becomes too sensitive to pain and other signals. Rather than being separate diseases, they might be related conditions caused by similar changes in how the brain and body communicate, combined with stress and emotional factors.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia syndrome in women.

Shaver, Joan L·The Nursing clinics of North America·2004

This article reviews fibromyalgia syndrome (FMS), a condition causing chronic pain and fatigue that affects far more women than men. The authors describe common symptoms and discuss research into what might cause FMS and related conditions like ME/CFS, IBS, and TMD, as well as current treatment options.

Pain and Sensitization
E3 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Applying exercise to the management of fibromyalgia.

Ambrose, Kirsten, Lyden, Angela K, Clauw, Daniel J·Current pain and headache reports·2003

This article reviews research on how exercise affects fibromyalgia and chronic fatigue syndrome. While medications are commonly used to treat these conditions, studies show that exercise can significantly reduce pain and tiredness. The authors suggest that exercise should be combined with other treatments as part of a comprehensive care plan.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Gender differences in fibromyalgia and other related syndromes.

Yunus, Muhammad B·The journal of gender-specific medicine : JGSM : the official journal of the Partnership for Women's Health at Columbia·2002

This review looked at why fibromyalgia and similar conditions like chronic fatigue syndrome affect many more women than men. Women with fibromyalgia tend to report more fatigue, worse sleep, more widespread pain, and more tender points than men. The reasons for these differences likely involve a mix of biological factors, psychological factors, and social factors.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryEditorialEditor reviewed

Somatization, sensitization, and functional dyspepsia.

Wilhelmsen, Ingvard·Scandinavian journal of psychology·2002

This study explores why people with conditions like ME/CFS, fibromyalgia, and functional dyspepsia experience overlapping symptoms such as fatigue, headaches, muscle pain, and sleep problems. The researchers suggest these different conditions may share a common underlying process where the nervous system becomes overly sensitive to pain and discomfort signals, leading the body to experience and report multiple symptoms across different areas.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Buskila, D·Current opinion in rheumatology·2001

This review examined fibromyalgia (FM), chronic fatigue syndrome (CFS), and related pain conditions across different countries. Researchers found that pain sensitivity involves brain chemistry (including a system called NMDA), hormone imbalances, and nervous system problems. CFS was found in about 0.4% of a large community sample, with many children recovering well, though the study notes that no major new treatments were tested during this period.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Sensitization, subjective health complaints, and sustained arousal.

Ursin, H, Eriksen, H R·Annals of the New York Academy of Sciences·2001

This study proposes that a process called 'sensitization'—where the body becomes increasingly reactive to triggers over time—may underlie many chronic conditions including ME/CFS, fibromyalgia, and chemical sensitivities. The authors suggest that prolonged stress and sustained arousal (keeping your nervous system in a heightened alert state) may make the body more likely to develop this sensitization, particularly affecting muscles and pain perception.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Pain complaints in patients with fibromyalgia versus chronic fatigue syndrome.

Bradley, L A, McKendree-Smith, N L, Alarcón, G S·Current review of pain·2000

Both fibromyalgia (FM) and ME/CFS cause muscle and joint pain, but the underlying reasons differ between these conditions. People with FM alone have unusually sensitive pain responses to light touch or mild pressure (called allodynia), while people with ME/CFS do not typically show this. This study examined what brain and hormone system differences might explain why these two conditions cause pain in different ways.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Buskila, D·Current opinion in rheumatology·2000

This review article examines the connections between fibromyalgia, chronic fatigue syndrome (ME/CFS), and myofascial pain syndrome. Researchers found that people with these conditions often have tender points in their muscles, hormonal imbalances affecting stress response, and possible immune system involvement. The study suggests that talking therapies like cognitive behavioral therapy may help manage chronic pain in these conditions, and that children and adolescents with these illnesses often improve over time.

Pain and SensitizationAutonomic Nervous System
E3 PreliminaryPEM unclearWeak / uncertainReview-NarrativeEditor reviewed

[Fibromyalgia in the year 2000].

Maquet, D, Croisier, J L, Crielaard, J M·Revue medicale de Liege·2000

This review article examines fibromyalgia (FM), a condition causing widespread muscle pain that affects about 2% of people. While doctors can diagnose fibromyalgia using a specific test (checking for tenderness at 18 specific body points), scientists still don't fully understand what causes it. This article summarizes what researchers knew in 2000 about how fibromyalgia develops and how doctors treat it.

Pain and Sensitization
E3 PreliminaryPEM unclearWeak / uncertainEditorialEditor reviewed

[Fibromyalgia syndrome].

Matsumoto, Y·Nihon rinsho. Japanese journal of clinical medicine·1999

This paper discusses fibromyalgia syndrome (FMS), a condition characterized by widespread pain, fatigue, sleep problems, and mood changes without visible inflammation or damage on tests. The author explains that while fibromyalgia is recognized as real, some doctors still debate whether it is truly distinct from other conditions. Many people with ME/CFS also meet the criteria for fibromyalgia, but there are some differences between the two conditions—such as signs of viral triggers and low blood chemical levels found in ME/CFS but not usually in fibromyalgia.

Pain and SensitizationSleep
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Patterns of waking EEG spectral power in chemically intolerant individuals during repeated chemical exposures.

Bell, I R, Szarek, M J, Dicenso, D R et al.·The International journal of neuroscience·1999

Some people experience discomfort or symptoms from exposure to low levels of chemicals and odors. This study measured brain electrical activity (EEG) in people with chemical intolerance before and after exposure to mild chemical odors across two sessions. Researchers found that people with chemical intolerance who had made major lifestyle changes showed different brain patterns than those who hadn't, suggesting the brain may become increasingly sensitive to these exposures over time.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Chronic orofacial muscle pain: a new approach to diagnosis and management.

Klineberg, I, McGregor, N, Butt, H et al.·The Alpha omegan·1998

This study looked at different types of muscle pain conditions, including fibromyalgia and jaw pain, and found they affect men and women differently. The researchers suggest that some people may be genetically vulnerable to chronic pain, and that infections at the start of illness might play a role. They found links between abnormal fat levels, muscle metabolism problems, and fibromyalgia, which may also be connected to chronic fatigue syndrome.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Fibromyalgia, chronic fatigue syndrome, and myofascial pain.

Bennett, R·Current opinion in rheumatology·1998

This review examines how fibromyalgia, chronic fatigue syndrome, and widespread pain are related conditions that share similar features. Researchers found that these conditions run in families, involve abnormal pain processing in the nervous system, and may share some underlying biological problems like growth hormone imbalances and low blood pressure. Several medications and treatments showed promise in reducing symptoms.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Neurobehavioral properties of chemical sensitivity syndromes.

Weiss, B·Neurotoxicology·1998

This review examines four conditions that involve chemical sensitivity and fatigue-like symptoms: Multiple Chemical Sensitivity Syndrome, Sick Building Syndrome, Chronic Fatigue Syndrome, and Gulf War Syndrome. The authors explore different theories about why people develop these conditions, including psychiatric factors, learned behavioral responses, changes in how the nervous system works, and problems with the immune system's stress response. The review suggests that laboratory studies and controlled clinical trials could help determine which explanations are correct.

Endocrine DisruptionPain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

[Multiple chemical sensitivity disorder in patients with neurotoxic illnesses].

Lohmann, K, Pröhl, A, Schwarz, E·Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))·1996

This study looked at 466 people who had neurological symptoms from toxic chemical exposure and found that 136 of them also had Multiple Chemical Sensitivity (MCS)—a condition where people react strongly to low levels of chemicals. The researchers found that wood preservatives, solvents, and formaldehyde were common culprits, and people with MCS were more likely to have chronic fatigue symptoms and allergies than those without MCS.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryEditorialEditor reviewed

Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.

Goldenberg, D L·Current opinion in rheumatology·1991

This review examines three related conditions—fibromyalgia, chronic fatigue syndrome, and myofascial pain—that often occur together and cause pain, tiredness, and sleep problems. Researchers are discovering that these conditions may share common biological causes involving how the body senses pain, hormone imbalances, and problems with muscle function. Unfortunately, the new treatments being tested at that time were not particularly effective.

Pain and SensitizationSleepDiagnostics
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Depression and chronic fatigue in the patient with chronic pain.

Covington, E C·Primary care·1991

This study explores how chronic pain, fatigue, and depression often occur together in patients. The authors suggest that these three conditions share common causes and may influence each other. Treatment works best when doctors address each problem separately using a combination of physical rehabilitation, education, medications, and counseling.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.

Tirelli, U, Valdenassi, L, Franzini, M et al.·European review for medical and pharmacological sciences·2023

This study looked at six breast cancer patients taking a hormone therapy drug (anastrozole) who experienced severe pain, weakness, and fatigue as side effects. These patients received oxygen-ozone therapy, a treatment where blood is mixed with ozone gas and returned to the body. After treatment, patients reported significant reductions in both pain and fatigue that lasted for several months.

Pain and Sensitization
E3 PreliminaryPEM not requiredModerate confidenceMechanisticEditor reviewed

Does muscular or mental fatigue have an influence on the nociceptive flexion reflex? A randomized cross-over study in healthy people.

Dhondt, Evy, Danneels, Lieven, Rijckaert, Johan et al.·European journal of pain (London, England)·2021

This study tested whether being physically or mentally tired changes how the body's spinal cord responds to pain signals. Researchers measured a reflex that happens in the spinal cord when stimulated with electrical pulses to a nerve in the leg, both before and after participants either rested, did tiring leg exercises, or completed a difficult mental task. They found that low-to-moderate levels of fatigue—whether physical or mental—did not change this spinal reflex, suggesting the body's pain-dampening systems stay stable even when tired.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryRCTEditor reviewed

Treatment for Gulf War Illness (GWI) with KPAX002 (methylphenidate hydrochloride + GWI nutrient formula) in subjects meeting the Kansas case definition: A prospective, open-label trial.

Holodniy, Mark, Kaiser, Jon D·Journal of psychiatric research·2019

Researchers tested a combination treatment called KPAX002—containing a stimulant medication (methylphenidate) plus vitamins and nutrients meant to support energy production in cells—in 17 people with Gulf War Illness. After 12 weeks, patients reported about 25% improvement in their overall symptoms, including better fatigue, brain fog, sleep, and pain. The treatment was generally safe and well-tolerated, though a larger, more rigorous study is needed to confirm these results.

Pain and SensitizationSleepCognitive Impairment
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

Fibromyalgia: A Critical and Comprehensive Review.

Borchers, Andrea T, Gershwin, M Eric·Clinical reviews in allergy & immunology·2015

Fibromyalgia is a condition that causes widespread pain, fatigue, and sleep problems, and it shares many symptoms with other conditions that are hard to diagnose. This review explains that while some people think fibromyalgia might be caused by infection, inflammation, or injury, there is not strong evidence supporting these ideas. The authors recommend that treatment should focus on education, exercise, physical therapy, and approved medications rather than opioids.

Pain and SensitizationSleepDiagnostics
E3 PreliminaryPEM unclearWeak / uncertainReview-NarrativeEditor reviewed

[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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

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 PreliminaryPEM not requiredWeak / uncertainObservationalEditor reviewed

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 PreliminaryPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

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 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Resting muscle pain as the first clinical symptom in children carrying the MTTK A8344G mutation.

van de Glind, Gretha, de Vries, Maaike, Rodenburg, Richard et al.·European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society·2007

This study describes children in a family who carried a specific genetic mutation in their mitochondria (the energy-producing parts of cells) and presented with muscle pain as their first symptom. The researchers found that muscle pain combined with fatigue in children can sometimes be mistakenly labeled as fibromyalgia or chronic fatigue syndrome, when the real cause is actually a rare inherited mitochondrial disorder called MERRF syndrome.

Pain and Sensitization
E3 PreliminaryPEM not requiredWeak / uncertainReview-NarrativeEditor reviewed

Fibromyalgia syndrome: a review.

Reiffenberger, D H, Amundson, L H·American family physician·1996

Fibromyalgia syndrome is a chronic condition characterized by widespread pain, stiffness, and tender points in muscles and soft tissues, often accompanied by fatigue and sleep problems. It affects women more than men, typically starting around age 49. Treatment combines medication (like certain antidepressants), education, reassurance, and exercise to help manage symptoms.

Pain and SensitizationSleep
E3 PreliminaryPEM not requiredPreliminaryEditor reviewed

'Repetitive strain injury': from Australia to the UK.

Reilly, P A·Journal of psychosomatic research·1995

In the 1980s, Australia experienced a widespread outbreak of upper limb pain that didn't fit standard medical diagnoses. The UK is now seeing a similar epidemic. This study examines whether the condition is truly caused by workplace activities or whether psychological and social factors play a larger role, similar to what happens in chronic fatigue syndrome.

Pain and Sensitization
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

Development of multiple chemical sensitivity after an outbreak of sick-building syndrome.

Welch, L S, Sokas, R·Toxicology and industrial health·1992

When workers were exposed to problems in a building (sick-building syndrome), some developed multiple chemical sensitivity (MCS)—a condition where people react to low levels of chemicals. This study looked at 20 people affected by the outbreak and found that most had existing health conditions like allergies or asthma that got worse. Importantly, having ME/CFS did not predict who would develop MCS, and many people had ongoing problems beyond just MCS after leaving the building.

Pain and Sensitization
E0 ConsensusPEM unclearModerate confidenceReview-NarrativeMachine-drafted

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.

Pain and SensitizationSleep
E2 ModeratePEM unclearPreliminaryObservationalMachine-drafted

Effect of noise stress on chronic fatigue syndrome patients.

Beh, H C·The Journal of nervous and mental disease·1997

This study looked at how noise affects people with ME/CFS, examining whether environmental sounds make their symptoms worse. The research observed how patients responded to noise stress as part of understanding the condition better. This type of research helps identify triggers that may worsen fatigue and other ME/CFS symptoms.

Pain and Sensitization
E2 ModeratePEM unclearPreliminaryCross-SectionalMachine-drafted

The localization of pain in chronic fatigue syndrome on a pain drawing according to grid areas.

Líndal, E, Bergmann, S, Thorlacius, S et al.·Perceptual and motor skills·1996

This study looked at where people with ME/CFS experience pain by having them mark painful areas on a body diagram divided into sections. The researchers wanted to understand the pattern of pain locations across different body regions in ME/CFS patients. This type of mapping can help doctors better understand how pain is distributed in the condition.

Pain and Sensitization
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeMachine-drafted

The Interplay between Oxidative Stress, Exercise, and Pain in Health and Disease: Potential Role of Autonomic Regulation and Epigenetic Mechanisms.

Hendrix, Jolien, Nijs, Jo, Ickmans, Kelly et al.·Antioxidants (Basel, Switzerland)·2020

This review examines how physical activity, pain, and a harmful process called oxidative stress (cellular damage from unstable molecules) interact in both healthy people and those with chronic pain conditions. The authors found that the relationships between these three factors are complicated and depend on the type of exercise and which person is being studied. They suggest that the nervous system's automatic functions and changes in how genes are expressed may help explain why these connections work differently in different people.

Pain and SensitizationAutonomic Nervous System

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