Evidence browser

Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome.

Yasui, Masaya, Menjyo, Yuki, Tokizane, Kyohei et al.·Journal of neuroinflammation·2019

This study used rats exposed to chronic stress to understand why ME/CFS patients experience widespread pain without obvious tissue damage. Researchers found that stress caused sensory nerve fibers (proprioceptors) that detect body position to become overactive, which then triggered immune cells in the spinal cord called microglia to activate and cause pain. When they immobilized the ankle to reduce proprioceptor signaling, both the immune activation and pain behavior decreased.

Neuroinflammation disorders exacerbated by environmental stressors.

O'Callaghan, James P, Miller, Diane B·Metabolism: clinical and experimental·2019

This review examines how inflammation in the brain and nervous system may be involved in ME/CFS and similar conditions. The authors suggest that various environmental stressors—like infections or other physical demands—can trigger or worsen this brain inflammation, leading to symptoms like fatigue, muscle pain, and brain fog. They propose that stress affects a key hormone system in the body (the HPA axis), which may play a role in how long these symptoms persist.

E3 PreliminaryReviewPEM requiredReview-Narrative

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods.

VanElzakker, Michael B, Brumfield, Sydney A, Lara Mejia, Paula S·Frontiers in neurology·2018

This review examines different methods scientists use to look for signs of brain inflammation in ME/CFS, including specialized brain scans and blood tests. The authors found that while these techniques show promise, many studies have used inconsistent methods that make it hard to compare results across different research teams. They argue that scientists need better techniques and more careful standardization if we want to find reliable biological markers that could help diagnose ME/CFS.

NeuroinflammationBiomarkers

Tetramethoxyluteolin for the Treatment of Neurodegenerative Diseases.

Theoharides, Theoharis C, Tsilioni, Irene·Current topics in medicinal chemistry·2018

This review examines how certain molecules in the brain called cytokines and neuropeptides may trigger inflammation in specific brain areas (the hypothalamus and amygdala) in people with ME/CFS. The authors propose that a natural compound called tetramethoxyluteolin (a modified form of a plant-derived substance called luteolin) might help reduce this inflammation and improve symptoms. The study suggests this compound could be delivered directly into the nasal passages to reach the brain more effectively.

Stress, inflammation and natural treatments.

Theoharides, T C, Kavalioti, M·Journal of biological regulators and homeostatic agents·2018

This study explores how stress and inflammation work together to cause several conditions including ME/CFS, fibromyalgia, and others. The researchers found that immune cells called mast cells and brain cells called microglia may communicate in ways that trigger inflammation during stress. They suggest that a natural supplement combining luteolin and Ashwagandha might help reduce this inflammation and benefit patients with these conditions.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Hatziagelaki, Erifili, Adamaki, Maria, Tsilioni, Irene et al.·The Journal of pharmacology and experimental therapeutics·2018

This study proposes that ME/CFS may be caused by inflammation in a small brain region called the hypothalamus, triggered by problems with how cells produce energy. The researchers suggest that when mitochondria (the energy factories in cells) malfunction, they may release harmful substances that activate immune cells in the brain, creating a chain reaction that leads to ME/CFS symptoms. If this theory is correct, it could open new doors for treating the condition by targeting this brain inflammation.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome.

Noda, Mami, Ifuku, Masataka, Hossain, Md Shamim et al.·Frontiers in psychiatry·2018

This review examines how brain inflammation might cause ME/CFS symptoms. When the body fights off a viral infection, special immune cells in the brain called microglia and astrocytes can become overactive and trigger a chain of events that reduces serotonin levels—a chemical important for mood and energy. Understanding this pathway could help researchers develop new treatments for ME/CFS.

[Brain Science on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

Watanabe, Yasuyoshi·Brain and nerve = Shinkei kenkyu no shinpo·2018

This study examined the brains of people with ME/CFS using three types of imaging technology (PET scans, MRI, and MEG) to look for physical differences compared to healthy people. Researchers found that people with ME/CFS have reduced blood flow and energy use in certain brain areas, decreased levels of important chemical messengers, and inflammation in the brain that appears connected to symptom severity. These findings suggest ME/CFS involves real, measurable brain changes rather than being purely psychological.

[Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)].

Yamamura, Takashi, Ono, Hirohiko, Sato, Wakiro·Brain and nerve = Shinkei kenkyu no shinpo·2018

This study found that people with ME/CFS have unusual patterns of immune system chemicals (cytokines) in their blood and spinal fluid, and some patients have antibodies that attack their own bodies. When researchers treated some ME/CFS patients with a medication that removes certain immune cells called B cells, patients improved. This suggests that ME/CFS may be caused by the immune system mistakenly attacking the body.

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

Morris, Gerwyn, Berk, Michael, Puri, Basant K·Molecular neurobiology·2018

This review compared brain imaging findings across three conditions—multiple sclerosis, depression, and ME/CFS—looking for similarities that might suggest a common underlying cause. The researchers found that all three conditions show similar patterns of brain abnormalities, including problems with blood flow to the brain and changes in brain structure. They suggest that inflammation and immune cell dysfunction in the brain may explain why patients with these different diagnoses have comparable brain imaging problems.

E3 PreliminaryMechanismPEM unclearObservational

[Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

Nakatomi, Yasuhito, Kuratsune, Hirohiko, Watanabe, Yasuyoshi·Brain and nerve = Shinkei kenkyu no shinpo·2018

Researchers used a special imaging scan called PET to look at the brains of people with ME/CFS and found signs of inflammation (immune system activation) throughout several brain regions. This inflammation was connected to how severe patients' symptoms were, including problems with thinking and memory, as well as widespread pain. This discovery suggests that ME/CFS involves measurable changes in the brain that could eventually lead to better ways to diagnose and treat the condition.

NeuroinflammationBiomarkers

NeuroinflammationBiomarkers

[History of Researches on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

Watanabe, Yasuyoshi, Kuratsune, Hirohiko·Brain and nerve = Shinkei kenkyu no shinpo·2018

This review summarizes research on ME/CFS conducted in Japan since the disease was first identified there in 1990. Scientists have been searching for objective biological markers to help diagnose ME/CFS and understand what causes it. Recent brain imaging studies found evidence of immune cell activation in the brains of ME/CFS patients, which may be linked to the severity of their symptoms.

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.

Morris, Gerwyn, Berk, Michael, Klein, Hans et al.·Molecular neurobiology·2017

This study proposes that ME/CFS may be caused by a harmful process called 'hypernitrosylation,' where a molecule called nitric oxide damages proteins in cells, particularly those responsible for producing energy and fighting infections. When this damage becomes chronic, it can disable the body's natural repair systems and trigger the immune system to attack the body's own proteins. The researchers suggest this process could explain many ME/CFS symptoms, including fatigue, cognitive problems, and how bacterial toxins may trigger or worsen the disease.

The Neuroinflammatory Etiopathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Glassford, Julian A G·Frontiers in physiology·2017

This article reviews research suggesting that ME/CFS may result from problems in how the nervous system and immune system interact. The author discusses how physical strain on the spine and nerves, combined with prolonged infections and immune activation, may trigger a chain reaction of inflammation in the brain and throughout the body. This inflammation can affect energy production, hormone balance, and how the body processes pain.

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity.

Crépeaux, Guillemette, Eidi, Housam, David, Marie-Odile et al.·Toxicology·2017

This study gave mice different amounts of aluminum hydroxide (a substance used in vaccines) injected into muscle and then checked their brains 6 months later. Surprisingly, the mice that received the lowest dose showed cognitive and movement changes, increased immune cell activity in the brain, and accumulated more aluminum in their brains—while the mice given higher doses did not. This unusual pattern suggests that aluminum's harmful effects may not simply follow the traditional "more dose = more harm" rule.

E3 PreliminaryCohortPEM not requiredCase-Control

CNS findings in chronic fatigue syndrome and a neuropathological case report.

Ferrero, Kimberly, Silver, Mitchell, Cocchetto, Alan et al.·Journal of investigative medicine : the official publication of the American Federation for Clinical Research·2017

This study examines brain tissue from one person who had ME/CFS and died, looking for physical changes that might explain the illness. Researchers found several abnormalities in the brain including areas of damaged nerve fibers, tangles similar to those seen in Alzheimer's disease, and deposits of a protein called amyloid. These findings suggest that ME/CFS may involve damage to the brain's structure and deserve further investigation.

NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation.

Zhang, Ziteng, Ma, Xiujuan, Xia, Zhenna et al.·Neuroscience·2017

This study explored whether a specific immune system protein called NLRP3 might be involved in causing fatigue in mice. Researchers stressed mice with repeated swimming tests and found that stressed mice had higher levels of an inflammatory chemical (IL-1β) in their brains and showed fatigue-like behaviors. When they removed the NLRP3 protein in mice, the fatigue behaviors were reduced and inflammatory levels decreased, suggesting this protein may play a role in fatigue.

E3 PreliminaryReviewPEM not requiredReview-Narrative

The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders.

Morris, Gerwyn, Carvalho, André F, Anderson, George et al.·Current pharmaceutical design·2016

When the body has chronic inflammation and immune activation, it breaks down an amino acid called tryptophan differently than usual, creating byproducts called TRYCATs. Some of these byproducts can damage nerve cells and mitochondria (the energy factories in cells), while others may protect the brain but at the cost of causing brain fog and emotional problems. This review examines how this abnormal tryptophan breakdown might contribute to ME/CFS and other neurological conditions.

NeuroinflammationEnergy MetabolismImmune System

Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

Zhang, Zi-Teng, Du, Xiu-Ming, Ma, Xiu-Juan et al.·Journal of neuroinflammation·2016

Researchers created a mouse model of fatigue by exposing mice to immune stress (a bacterial compound) combined with physical stress. They found that a specific immune protein called NLRP3 becomes active in the brain during fatigue, and that blocking this protein reduced fatigue symptoms. This suggests that controlling this immune pathway might help treat fatigue in conditions like ME/CFS.