Many doctors believe that fibromyalgia may be an autoimmune disease in which the immune system mistakenly attacks healthy cells. However, the evidence gathered for years seemed to dispute that belief. Now, new research suggests that FM may be an autoimmune disease involving neuroinflammation, which is an inflammatory response within the brain and spinal cord. It may also involve neuropathy, which is pain and weakness from nerve damage.
Is fibromyalgia an autoimmune disease?
For decades, FM was controversial. Some doctors believed it was similar to arthritis. Others suspected autoimmunity because of its similarities to autoimmune diseases like multiple sclerosis, rheumatoid arthritis, and lupus.
However, prior research could not find the common signs of an autoimmune disease such as:
- Damage from the immune system attack
- Inflammation as part of the immune and healing processes
- Autoantibodies (immune system proteins that target a part of your body)
What is autoimmunity?
Autoimmunity is an immune system turned against its body. Your immune system mistakes a healthy type of cell or tissue in your body for a dangerous pathogen, like a virus or bacterium. It then attacks and tries to destroy the target. This leads to tissue damage, inflammation, and other symptoms.
More recently, doctors considered FM to be a pain condition that was neurological or neuro-immune. Soon, an umbrella term became common: central sensitivity syndrome, which encompassed FM and related illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), irritable bowel syndrome (IBS), and migraine.
Now, FM is seen as a complex, multi-symptom illness. And, researchers are discovering more evidence that FM does in fact include the common signs of an autoimmune disease like:
What’s more, evidence is mounting that it actually isn’t missing those hallmarks of autoimmunity:
- Small-fiber neuropathy
- Inflammation in the brain and nerves of the spinal cord
- Autoantibodies
- Autoimmunity
Fibromyalgia has always seemed similar to autoimmune diseases. Research published in 2019 detailed the many factors they have in common:
- Frequently triggered by trauma and infection
- Various pathogens may increase your risk (Epstein-Barr virus, herpes simplex virus, hepatitis C)
- They can develop soon after vaccination, silicone breast implantation, or mineral oil injection
- More common in women
- Involve genetic differences known to predispose you to autoimmunity
- Often occur alongside other autoimmune disease.
- Evidence shows activation of the adaptive immune system
- Autoantibodies
New research suggests clear signs of autoimmunity in FM. Scientists have found that several autoantibodies were unusually high in people with FM, including:
- Serotonin: A neurotransmitter (chemical messenger) and hormone known to be dysregulated in FM
- Gangliosides: A type of molecule in the brain linked to several neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and
- amyotrophic lateral sclerosis (ALS)3
- Phospholipids: Molecules that make up protective barriers around cells and regulate certain cellular processes
- Smooth muscle: Muscles located in organs, under involuntary control
- Striated muscle: Skeletal muscles, under voluntary control
- Moisture-producing glands: The same autoantibodies as in Sjögren’s syndrome, which affect moisture-producing glands in the mucous membranes,
- which line organs and the inside of your body
- Thyroid gland: The same autoantibodies as in Hashimoto’s thyroiditis, an autoimmune thyroid disease
The prevalence of these markers varied between the study participants. The rates ranged from 19% to 73%:
- Serotonin, 73%
- Gangliosides, 71%
- Phospholipids, 54%
- Smooth muscle, 55%
- Striated muscle, 40%
- Sjögren’s syndrome antibodies, 32%
- Thyroid gland, 19%
Giving fibromyalgia to mice
In an important study conducted just this year, researchers collected antibodies (immunoglobulin G, IgG) from people with FM and injected them into mice. The mice then:
- Developed hypersensitivity to pain and cold
- Became less active
- Lost paw grip strength
- Lost nerve fibers in the skin
Researchers say the FM IgG appeared to target white-matter brain cells (glia), gray-matter brain cells (neurons), and certain nerve fibers. This shows how immune system activity can cause neurological symptoms.
Transferring FM in this way was groundbreaking. It may lead to the development of new diagnostic tests and treatments.
Diagnosis and treatment
If more research validates findings of autoimmunity in fibromyalgia, it could lead to diagnostic tests. For a condition that’s currently a diagnosis of exclusion, that’s an important change.Many immunosuppressive drugs for autoimmune diseases are already on the market. That greatly expands treatment options, especially since the drugs could be used off-label right away.
Neuroinflammation
Several studies have now confirmed neuroinflammation in fibromyalgia. Some also have looked at where it is in the brain and what may be driving it.
Inflammation is a complex immune response to injury and infection. When it becomes chronic, inflammation causes tissue damage. It’s especially harmful in the nervous system. The immune system and the nervous system work to create neuroinflammation. Now, FM studies have found links to certain cells and one specific molecule involved in the process.
Neurological components include:
Microglia: A type of cell that’s part of the nervous system’s dedicated immune system
- Astrocytes: Cells of the brain and spinal cord involved in information processing and implicated in neurodegenerative disease
- Oligodendrocytes: White-matter cells that form myelin sheaths around nerves and regulate neuronal circuits
- Brain-derived neurotrophic factor (BDNF): A key molecule involved in learning and memory, also tied to aging and brain-related disease
Immune system components include:
- Mast cells: A type of white blood cell that helps keep the immune system in balance
- Chemokines: Immune cells that attract white blood cells to sites of infection
- Proinflammatory cytokines: Immune system proteins that drive the inflammatory response
- Interleukins: Proteins that regulate immune response
- Tumor necrosis factor alpha (TNFα): A type of cytokine involved in inflammation and cell death
- Macrophages: Tissue resident immune cells usually found at the site of infection
- T-cells: Specialized immune cells that target proteins identified (or misidentified) as foreign
Another study conducted this year examined the location of brain inflammation in people with FM. Scientists found several regions with abnormal inflammation versus healthy people in the control group. Some of these regions perform key roles in the functions that are frequently dysregulated in people with FM. These include:
- Primary somatosensory cortex: Processes physical sensations, especially touch
- Primary motor cortex: Skilled movement
- Superior frontal gyrus: Higher cognitive function and working memory
- Left superior parietal gyrus: Attention, spatial perception
- Left precuneus: Memory-based tasks, episodic memory recall
- Left medial frontal gyrus: Development of literacy
They study also found abnormally low inflammation-related activity in the:
- Medulla: Relays messages between your brain and spinal cord, regulates cardiovascular and respiratory systems (heart and lungs)
- Amygdala: Drives the stress and fear response (fight-or-flight)
- Left superior temporal gyrus: Language processing, remembering what you’ve just heard
Neuroinflammation in the amygdala, left medial frontal, and left superior parietal gyri was associated with higher pain scores. Neuroinflammation in the left amygdala, left medial frontal, and left superior frontal gyri was associated with higher stress responses, which included measures of fatigue, tension, frustration, depression, somatization, and aggression.
Diagnosis and treatment
Inflammatory markers for fibromyalgia tend to be slightly elevated. But the cells and molecules involved in the neuroinflammation of FM may provide new diagnostic markers to look for. Drugs that suppress microglia and astrocytes may be useful for treating neuroinflammation. They include:
- Low-dose naltrexone (LDN)
- Diamox (acetazolamide)
- Trental/Pentoxil (pentoxifylline)
- Zirgan (ganciclovir)
- Rifadin (rifampin)
- Enbrel (etanercept)
- Precedex (dexmedetomidine)
- Delsym/Robitussin (dextromethorphan)
- Propentofylline (an experimental drug)
- Dynacin/Minocin/Solodyn (minocycline)
- Cannabidiol (CBD)
- P2X7R inhibitors (experimental drugs)
Other existing treatments for neuroinflammation include:
- Tricyclic antidepressants, including amitriptyline and nortriptyline20
- Low-dose corticosteroids
- Nutritional supplements, including vitamin B12
- Hormonal supplementation, including oxytocin, human growth hormone, and human chorionic gonadotropin
Several other drugs are under development for neuroinflammation, most of them developed as potential Parkinson’s disease treatments. Anti-inflammatory drugs are often prescribed for neuroinflammation as well. However, they’ve historically been considered ineffective for FM pain.
Small-fiber neuropathy
Small-fiber neuropathy (SFN) is nerve damage that’s only in the small sensory nerves of the skin. It’s probably best known in relation to type 2 diabetes. As in FM, the pain comes and goes and is described as:
- Stabbing
- Burning
- Tingling
- Itchy
Also like FM, SFN involves the abnormal pain types hyperalgesia and allodynia. Hyperalgesia makes your pain signals more intense, basically “turning up the volume” of pain. Allodynia makes things hurt that shouldn’t, like a loose waistband or a hand rubbing lightly against your skin.
The 7 types of fibromyalgia pain
SFN and fibromyalgia also have these symptoms in common:
- Pain triggered by heat or cold
- Urinary problems
- Bowel problems
- Periodic rapid heartbeat
- Dry eyes and/or mouth
- Abnormal sweating
- Orthostatic intolerance (dizziness from a sharp drop in blood pressure upon standing)
FM research suggests some damaged nerves are part of anti-inflammatory processes. That provides another explanation for neuroinflammation.1
Typical SFN vs. fibromyalgia SFN
In most SFN, pain begins in the feet and then moves upward. Whole body pain is not typical with SFN, but is more common in FM.
Diagnosis and treatment
The typical diagnostic test for SFN is a skin punch biopsy. A small amount of skin is removed with a circular tool and examined under a microscope. The focus is on nerve fiber density in the skin. SFN is treatable, and small nerves continue to grow throughout life. That means they can repair damage.
Standard SFN treatments are frequently used for fibromyalgia. These include:
- Anti-seizure medications: Lyrica (pregabalin), Neurontin (gabapentin)
- Serotonin-norepinephrine reuptake inhibitors: Cymbalta (duloxetine), venlafaxine
- Tricyclic antidepressants: Amitriptyline, nortriptyline, desipramine
In a pilot study, treatment with intravenous immunoglobulin (IVIg) has been shown to improve SFN in FM. This treatment is known to be effective against autoimmune-related neuropathy. Biopsies confirmed that nerves showed less damage after treatment.
Ganglioside autoimmunity may suggest treatment options as well. Gangliosides are suspected of being involved with diabetes-related small-fiber neuropathy. Some early animal research has suggested that ganglioside-targeted treatments may improve neuropathic pain.
Currently, researchers are working on drugs called ganglioside GM3 synthase inhibitors. Evidence suggests that these may work as both oral medication and topical treatments.
Final thoughts
New research has discovered evidence that FM may be an autoimmune disease. Key factors in FM include neuroinflammation and small-fiber neuropathy. This may lead to developments in which autoantibodies provide diagnostic markers for FM. Neuroinflammation and SFM may also be potential diagnostic markers. Treatments may include immunosuppressants and some experimental drugs that are currently being developed.