Fibromyalgia is complex and the root cause mechanisms are still poorly understood. Research into the role of glial cells in fibromyalgia has been ongoing. It’s an exciting and emerging area of study that needs more funding. Glial cells play essential roles in supporting and maintaining the function of neurons, which are the primary signaling cells in the nervous system. There are several types of glial cells, each with its own distinct functions.
The two main types of glial cells in the Central Nervous System:
- Astrocytes: Astrocytes are the most abundant type of glial cell in the CNS. They have various functions like providing physical and metabolic support to neurons, regulating the chemical environment around neurons by maintaining ion balance (e.g., potassium and calcium), forming the very crucial blood-brain barrier, which helps protect the brain from harmful substances in the bloodstream, and contribute to the repair of damaged neural tissue.
- Microglia: Microglia are the resident immune cells of the CNS. They play a crucial role in the brain’s immune response to infections, injury, or inflammation. Microglia can become activated in response to injury or disease, where they function in phagocytosis (the engulfing and removal of cellular debris) and release inflammatory mediators.
In addition to astrocytes and microglia, other types of glial cells include:
- Oligodendrocytes: Oligodendrocytes are responsible for producing myelin, a fatty substance that forms an insulating sheath around axons in the CNS. Myelin allows for faster transmission of electrical signals along nerve fibers.
- Schwann Cells: Schwann cells are the counterparts of oligodendrocytes in the PNS. They also produce myelin, which wraps around peripheral nerve fibers.
- Ependymal Cells: Ependymal cells line the cavities (ventricles) within the brain and the central canal of the spinal cord. They produce cerebrospinal fluid (CSF), which bathes and cushions the CNS.
Glial cells are essential for the proper functioning of the nervous system. While neurons are responsible for transmitting electrical signals, glial cells provide critical support, protection, and regulatory functions that help maintain a healthy and functioning nervous system. Research into the roles of glial cells is ongoing, and it has become increasingly clear that these cells play important roles in various neurological and neurodegenerative conditions, including those like fibromyalgia.
Here are some key findings related to the research on glial cells in fibromyalgia.
Role of Glial Cells in Pain Processing:
Research suggests that glial cells, particularly microglia and astrocytes, become activated in response to chronic pain conditions, including fibromyalgia. These activated glial cells release pro-inflammatory cytokines and other substances that can sensitize pain pathways.
Spinal glial activation can be considered an important component in the development and maintenance of allodynia and hyperalgesia in various models of chronic pain, including neuropathic pain and pain associated with peripheral inflammation. In addition, spinal glial activation is also involved in some forms of visceral hyperalgesia.
Bradesi S. Role of spinal cord glia in the central processing of peripheral pain perception. Neurogastroenterol Motil. 2010 May;22(5):499-511. doi: 10.1111/j.1365-2982.2010.01491.x. Epub 2010 Mar 16. PMID: 20236247; PMCID: PMC2893561.
Glial Neuronal Interaction READ HERE
Neuroinflammation and Fibromyalgia:
New fibromyalgia research studies have reported evidence of neuroinflammation in the brains of individuals living with fibromyalgia, which is thought to be linked to glial cell activation. Neuroinflammation may contribute to the hypersensitivity to pain and other sensory stimuli observed in fibromyalgia patients.
Evidence from PET scans shows inflammatory mechanisms in the brains of people with fibromyalgia, according to research published in a 2019 issue of the journal Brain, Behavior, and Immunity. This is a major step forward in understanding the underlying mechanisms. The study also shed light on a category of brain cells called glia and their role in fibromyalgia and suggests new avenues for treatment.
In this particular study, they did find that evidence using tracers showed microglial activation in numerous regions of the brain, which makes sense because the pain of fibromyalgia is widespread, not confined to any single area of the body. The brain regions that were involved included the:
- Dorsolateral prefrontal cortex
- Dorsomedial prefrontal cortex
- Primary somatosensory and motor cortices
- Posterior cingulate cortex
- Supplementary motor area
- Supramarginal gyrus
- Superior parietal lobule
- Possibly the anterior middle cingulate
Many of these brain regions have been shown to be abnormal in previous fibromyalgia neuroimaging studies. Researchers also found an association between high activity in several of these regions and severe fatigue. This was the first study to find direct evidence of neuroinflammation in fibromyalgia, and it also suggested the method by which the inflammation occurred. That means treatments for microglial overactivity can now be explored as possible therapies for the condition.
Symptoms of neuroinflammation vary depending on what region of the brain it’s in. A major neuroinflammation symptom that has been discovered through research is neurodegeneration.
Albrecht DS, Forsberg A, Sandstrom A, et al. Brain glial activation in fibromyalgia – a multi-site positron emission tomography investigation. Brain Behav Immun. 2019 Jan;75:72-83. doi:10.1016/j.bbi.2018.09.018
Marco L. Loggia, Daniel B. Chonde, Oluwaseun Akeju, Grae Arabasz, Ciprian Catana, Robert R. Edwards, Elena Hill, Shirley Hsu, David Izquierdo-Garcia, Ru-Rong Ji, Misha Riley, Ajay D. Wasan, Nicole R. Zürcher, Daniel S. Albrecht, Mark G. Vangel, Bruce R. Rosen, Vitaly Napadow, Jacob M. Hooker, Evidence for brain glial activation in chronic pain patients, Brain, Volume 138, Issue 3, March 2015, Pages 604–615, https://doi.org/10.1093/brain/awu377
Jo Nijs, Marco L. Loggia, Andrea Polli, Maarten Moens, Eva Huysmans, Lisa Goudman, Mira Meeus, Luc Vanderweeën, Kelly Ickmans & Daniel Clauw (2017) Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?, Expert Opinion on Therapeutic Targets, 21:8, 817-826, DOI: 10.1080/14728222.2017.1353603
Other studies have also highlighted the importance of understanding interactions between glial cells and neurons in the context of fibromyalgia. Abnormal signaling between glia and neurons may contribute to the pathophysiology of the condition.
Potential Therapeutic Targets:
Research into glial cell function in fibromyalgia has raised the possibility of developing targeted therapies that modulate glial cell activity to alleviate symptoms. Drugs that inhibit glial cell activation are being explored as potential treatments for fibromyalgia.
It’s important to note that research on the role of glial cells in fibromyalgia is ongoing, and the exact mechanisms and implications of glial cell involvement are still being elucidated. Additionally, while there is evidence suggesting a connection between glial cell activation and fibromyalgia, further research is needed to fully understand this relationship and its potential therapeutic implications.
Jung, Changjina,b; Ichesco, Ericc; Ratai, Eva-Mariaa,d; Gonzalez, Ramon Gilbertoa,d; Burdo, Triciae; Loggia, Marco L.a,d; Harris, Richard E.c; Napadow, Vitalya,d,f,*. Magnetic resonance imaging of neuroinflammation in chronic pain: a role for astrogliosis?. PAIN 161(7):p 1555-1564, July 2020. | DOI: 10.1097/j.pain.0000000000001815
Seo, S., Jung, Y. H., Lee, D., Lee, W. J., Jang, J. H., Lee, J. Y., … & Kang, D. H. (2021). Abnormal neuroinflammation in fibromyalgia and CRPS using [11C]-(R)-PK11195 PET. PloS one, 16(2), e0246152.
Bäckryd E, Tanum L, Lind AL, Larsson A, Gordh T. Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. J Pain Res. 2017;10:515-525
Listen to Dr. Marco Loggia’s presentation on neuroinflammation from critical fibromyalgia research!