Microglia in Fibromyalgia and Chronic Fatigue Syndrome

Exploring the Brain's White Matter

Illustration shows glial fibers in the human brain. Pasieka/Getty Images

Microglia are tiny cells in the central nervous system (CNS), which consists of your brain and spinal cord. While they're small, they have a major role to play: they're the first line of defense in the CNS's dedicated immune system.

The term "glia" literally means "glue." Glial cells come in multiple forms and perform multiple different support function for neurons, including the clean-up of used chemicals (a process called reuptake) and insulating neurons (as myelin sheaths), which is essential for them to function properly.

(Damage to myelin sheaths is a key feature of multiple sclerosis.)

Micro means "small," so "microglia" literally means small glial cells.

Microglia 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 are 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, microglia 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.

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.

Hyperalgesia is the amplification of pain by the central nervous system, essentially "turning up the volume." It's why an injury hurts especially bad, and back pain you've had since before you were chronically ill became worse when fibromyalgia or chronic fatigue syndrome hit.

Allodynia is pain from something that normally doesn't cause pain. Mechanical allodynia is pain caused specifically by movement. That means gentle massage or something as little as the brush of clothing against your skin can cause intense pain.

Other research suggests that microglia is also involved in tactile allodynia (pain from light pressure, such as a waistband) and may contribute to or cause pain by mechanisms other than inflammation. (What these mechanisms are is something researchers have yet to work out.)

Genetic research in people with fibromyalgia points to the possibility that certain genes may contribute to pain by ramping up the activity of microglia in the spine.

These studies not only help us understand what's causing the symptoms of fibromyalgia and chronic fatigue syndrome but help us identify targets for future research and treatments. At least one drug that's believed to limit the activity of microglia—low-dose naltrexone—has received some research attention for these conditions. This drug is already on the market but so far has not been approved for use in these conditions, so it has to be prescribed off-label.

Sources:

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.