Microglia in Fibromyalgia and Chronic Fatigue Syndrome

Microglia in Fibromyalgia and Chronic Fatigue Syndrome

By: Dr Alex Robber

What are Microglia cells?

“It is not explicitly about what the FDA-approved drugs are looking for. Fibromyalgia is about central nervous system neuroinflammation [CNS], “said Younger, who is an associate professor of psychology and founder of the Neuroinflammation, Pain and Fatigue Lab at Birmingham University of Alabama.

“The secret to recovery is reducing the cycle of inflammation in the brain. We need to discover and use both therapeutic and other therapies that can enter the CNS and activate the inflammation-driven cells. Younger identified basic microglia cell states, which serve as the first type of active immune defense in the CNS, and how they respond to inflammation and pain.

“Microglia cells are special forces on the Green Beret brain. We contain hundreds of compounds that drive the CNS into an agitating, inflammatory condition, “he said. Microglia cells in fibromyalgia go from a resting state to an activated state and become hyper-excitable and over-express receptors.

Microglia and Brain Fog

Microglia may be one of the physiological factors involved in cognitive dysfunction in fibromyalgia and chronic fatigue syndrome (e.g. fibro fog or brain fog). Many researchers hypothesize that the presence of certain molecules in our brains may get microglia stirred up and active, which increases inflammation in the region and impairs how our brain functions in that place.

A 2014 study suggests that chronic microglial activation in the spine may be responsible for two forms of excessive pain in chronic fatigue syndrome, at least in part: muscle hyperalgesia, and mechanical allodynia. Both types of pain are also essential characteristics of fibromyalgia.

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Activation of microglia plays an important role in the pathogenesis of chronic pain

Microglia is the immune cells that live in the spinal cord and brain. Mounting evidence indicates microglia activation plays an important role in chronic pain pathogenesis including chronic orofacial pain. Microglia contributes to the transition from acute pain to chronic pain, as microglial signaling suppression decreases pathological pain following trauma, nerve injury, and cancer but not baseline pain.

Nerve damage causes much more robust morphological activation of microglia, called microgliosis compared to inflammation, as demonstrated by increased expression of microglial markers such as CD11b and IBA1. However, microglial signaling inhibitors effectively reduce inflammatory pain and neuropathic pain, arguing against the importance of microglia morphologic activation in the sensitization of chronic pain.

Importantly, microglia improve pain conditions through the secretion of proinflammatory and prognostic mediators, such as the tumor necrosis factor α, interleukins 1β and 18, and the growth factor generated from the brain. Mechanistically, it has been shown that these mediators enhance excitatory synaptic transmission and reduce inhibitory synaptic transmission in the circuits of pain.

Does Microglia Cause Chronic Pain and Fatigue?

Microglia covers our brains and spinal cord and protects the nerves. Such cells are the main immune defenders in the brain and are responsible for releasing chemicals that are infectious and neuro protective. These substances may cause symptoms of fatigue, pain and fogginess in the mind.

These symptoms can at times be debilitating for most patients. Some researchers believe that stress and infection can lead to hypersensitivity of the microglia causing neuroinflammation that can lead to conditions such as Chronic Fatigue Syndrome (ME / CFS) and Fibromyalgia (FMS).

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In a small study using PET scans to assess microglial activation, researchers found that the chronic fatigue syndrome patients had activated microglia in large areas of the brain. Researchers believe that microglial sensitization can be the cause of tiredness; they also believe that that microglial activity could boost ME / CFS and FMS.

Microglia cell primers

All leptin and glucose are important primers for the microglia cells. That is why diet can have an effect on inflammatory brain processes, he said. Leptin levels co-ordinatewith fibromyalgia pain and tiredness. “Leptin can act as a pathway to fibromyalgia and chronic fatigue syndrome pain and fatigue,” he said. Cell modulators for microglia include naltrexone, minocycline, ibudilast, and dextromethorphane.

“These drugs were created for other purposes and were later found to effectively suppress microglia cells and return them to a resting state or prevent them from triggering,” Younger said. Low doses of naltrexone block opioid receptors on microglia cells and toll-like receptor 4. Two clinical trials of 4.5-mg of naltrexone daily in females with fibromyalgia indicate an improvement after 2 months.

Most patients feel healthier, and slowly decline in their symptoms, Younger said. Side effects are few, with vivid dreams being the most common. “Naltrexone is functioning in the brain as a novel anti-inflammatory,” he said. “When we monitor inflammation over time, we see inflammatory processes having an effect.”

Microglia’s can move freely

Microglia’s can move around the brain and spinal column easily to areas where an injury or infection is present. We act as a warning system while there by alerting other parts of the immune system to the problem so that the body can try to fix it. And their jog is not finished once the alarm has been lifted. Microglia also represents an essential part of the answer to the problem.

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The microglial involvement, as with other forms of immune response, can contribute to inflammation. Inflammation is a required part of the healing process so it’s a good thing in that respect. But, if it becomes chronic, inflammation will lead to various health problems over and above pain and discomfort.

Microglia is a relatively new finding in medical science and there is a lot we still don’t learn about them. Evidence has however shown that they are involved in almost all neurological diseases.


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  • Yasui M, et al. Glia. 2014 Sep;62(9):1407-17. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation.
  • Microglia in Fibromyalgia and Chronic Fatigue Syndrome by Adriene Dellwo via Verywell Health

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