What are Microglia cells?
“It’s not about what the FDA-approved treatments directly target. Fibromyalgia is about neuroinflammation in the central nervous system [CNS],” said Younger, who is associate professor of psychology and director of the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama at Birmingham.
“The key to treatment is to reduce that inflammatory process in the brain. We have to discover and employ both pharmaceutical treatments and other interventions that can get to the CNS and target the cells that drive the inflammation.” Younger described the basic states of microglia cells, which act as the first form of active immune defense in the CNS, and how they relate to inflammation and pain.
“Microglia cells are the brain’s Green Beret special forces. They produce dozens of compounds that push the CNS into an inflammatory, excitatory state,” he said. In fibromyalgia, microglia cells go from a resting to a primed state and become hyper excitable and over express receptors.
Microglia and Brain Fog
In fibromyalgia and chronic fatigue syndrome, microglia may be one of many physiological factors involved in cognitive dysfunction (a.k.a. fibro fog or brain fog.) Some researchers hypothesize that the presence of certain molecules in our brains may get microglia stirred up and active, which increases inflammation in the area and impairs the way our brain functions in that spot.
A 2014 study suggests that chronic microglial activation in the spine may be responsible, at least in part, for two abnormal pain types in chronic fatigue syndrome: hyperalgesia in the muscles, and mechanical allodynia. Both of these pain types are key features of fibromyalgia as well.
Activation of microglia plays an important role in the pathogenesis of chronic pain
Microglia is the resident immune cells in the spinal cord and brain. Mounting evidence suggests that activation of microglia plays an important role in the pathogenesis of chronic pain, including chronic orofacial pain. In particular, microglia contributes to the transition from acute pain to chronic pain, as inhibition of microglial signaling reduces pathologic pain after inflammation, nerve injury, and cancer but not baseline pain.
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As compared with inflammation, nerve injury induces much more robust morphologic activation of microglia, termed microgliosis, as shown 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 morphologic activation of microglia in chronic pain sensitization.
Importantly, microglia enhances pain states via secretion of proinflammatory and pronociceptive mediators, such as tumor necrosis factor α, interleukins 1β and 18, and brain-derived growth factor. Mechanistically, these mediators have been shown to enhance excitatory synaptic transmission and suppress inhibitory synaptic transmission in the pain circuits.
Does Microglia Cause Chronic Pain and Fatigue?
Microglia surround and protect the neurons in our brains and spinal cord. These cells are the main immune defenders in the brain and are responsible for releasing inflammatory and neuro-protective substances. These substances may cause symptoms of fatigue, pain, and mental fogginess.
For most patients these symptoms can be crippling at times. Some researchers believe stress and infection can cause the microglia to become hypersensitive causing neuroinflammation that may result in conditions such as Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FMS).
In a small study that used PET scans to measure microglial activation, researchers found that microglia were activated in large areas of the brain of chronic fatigue syndrome patients. Researchers believe that microglial sensitization could be the cause of fatigue; they also believe reducing the activity of microglial could improve ME/CFS and FMS.
Microglia cell primers
Both leptin and glucose are potent microglia cell primers. That is why diet can impact inflammatory processes in the brain, he said. Leptin levels coordinate with the pain and fatigue of fibromyalgia. “Leptin may be a gateway to pain and fatigue in fibromyalgia and chronic fatigue syndrome,” he said. Microglia cell modulators include naltrexone, minocycline, ibudilast, and dextromethorphan.
“These drugs were developed for other purposes and subsequently were found to potently suppress microglia cells and get them back to resting state or prevent them from becoming activated,” Younger said. Low doses of naltrexone block opioid receptors and toll-like receptor 4 on microglia cells. Two clinical trials of 4.5-mg daily doses of naltrexone in women with fibromyalgia show an effect after 2 months.
Most patients feel better and their symptoms slowly decline, Younger said. Side effects are few, the most common being vivid dreams. “Naltrexone works as a novel anti-inflammatory in the brain,” he said. “If we track inflammation over time, we see an effect on inflammatory processes.”
Microglias are able to move freely
Microglias are able to move freely around the brain and spinal column to places where there’s an injury or infection. Once there, they serve as an alarm system by alerting other parts of the immune system to the problem so your body can try to fix it. Their jog isn’t done once the alarm is raised, though. Microglia is also an important part of the response to the problem.
As with other types of immune response, the microglial activity can lead to inflammation. Inflammation is a necessary part of the healing process, so in that way, it’s a good thing. If it becomes chronic, though, inflammation can lead to myriad health problems beyond just pain and discomfort.
In medical science, microglias are a relatively new discovery and there’s much we still don’t understand about them. However, research has shown that they’re involved in nearly all neurological disease.
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- Graeber MB, Christie MJ. Experimental neurology. 2012 Apr;234(2):255-61. Multiple mechanisms of microglia: a gatekeeper’s contribution to pain states.
- Light KC, et al. Pain research and treatment. 2012;2012:427869. Genetics and gene expression involving stress and distress pathways in fibromyalgia with and without comorbid chronic fatigue syndrome.
- Tambuyzer BR, Ponsaerts P, Nouwen EJ. Journal of leukocyte biology. 2009 Mar;85(3):352-70. Microglia: gatekeepers of central nervous system immunology.
- Theoharides TC, et al. Frontiers in neuroscience. 2015 Jul 3;9:225. Brain “fog,” inflammation and obesity; Key aspects of neuropsychiatric disorders improved by luteolin.
- 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