Understanding Brain Inflammation in Fibromyalgia Patients

Fibromyalgia (FM) is a common and complex chronic pain disorder that causes widespread pain and tenderness to touch that may occur in specific tender or trigger points or body wide.  

Symptoms of fibromyalgia are widespread and run the gamut of intensity. Symptoms like fatigue, sleep disturbances, cognitive difficulties and stiffness are the most often reported. Additional symptoms include depression, anxiety, migraines, tension headaches, pelvic pain, irritable or overactive bladder, irritable bowel syndrome (IBS), TMJ, and gastrointestinal reflux.  Stress increases the intensity of the symptoms and can be the culprit of a pain cycle that is impossible to manage. 

Those suffering from fibromyalgia typically have an increased reaction to outside stimulus.  There can be an increased autonomic response to mild day-to-day sensations such as sounds lights and odors. 

The latest research tends to indicate that this condition of hyper-sensation has something to do with the changes in the brain.

There is increasing evidence that due to various chronic stressful conditions, pain pathways in the brain are altered. A person living with fibro will often experience chronic headaches, visceral pains, and other painful conditions. 

Stressful life events, and physical or emotional trauma, cause the flare up of inflammatory responses, and these responses are communicated to the brain. If these stressful conditions continue for quite long, they result in changes in brain resulting in hyper-sensation syndrome.

Recently, there has been a much greater interest in looking at the cells of the brain that play a role in inflammation and hypersensitivity. One such cell known to play a central role in the inflammatory responses in the brain is microglia. 

Mechanisms of inflammation and neural involvement

Inflammation is a defensive mechanism. Once the body faces an infective agent, debris or other foreign material, inflammation occurs and chemicals from the body's white blood cells are released to protect your body from foreign substances.  Blood flow increases to the area of injury or infection. This protective process may stimulate nerves and cause pain.  Macrophages are cells that rid the body of worn-out cells and other debris. Along with dendritic cells, they play an important role in sending out an inflammatory response. 

The brain center initiates actions to elevate body temperature to prevent microbial growth. The brain tries to conserve energy by forcing us to rest, reduce social interaction, and physical activities, for example. . The brain is central to pain response. But how does the information exchange between the point of inflammation and brain occur? It happens through the messengers called cytokines, and through the input from the nerves.

Inflamed brain and fibromyalgia

We now know that the brain is not only involved in controlling our thoughts and emotions but is automatically engaged in managing the inflammatory responses to trauma, stress, and other threats. This defense mechanism involving local responses and changes in brain functioning have evolved over the millions of years of our evolution. Our body is impeccably made to give a proper reply to an acute threat.

During the last century or so, the environment and living conditions have changed faster than our body can adapt or evolve. The changed working condition, better treatment of many acute disorders, cancers, surgical therapies, have all contributed to chronic stress and inflammation. Our brain is continually under stress which has resulted in sensitization of various structures of the brain. This continual feedback to the brain results in sensitization of microglia that results in inflammatory responses, hyper-sensation, and hyper-reaction. It seems multiple defense mechanisms of our brain and body are not made to operate in this chronic fashion, giving rise to new types of health issues. 

Fibromyalgia and microglial connection

The chronic stressful condition makes specific brain cells hyper-responsive.  The result is increased levels of inflammatory factors, pain sensation, and mood changes like depression or anxiety.

To prove this hypothesis regarding the hyperactivity of the microglia brain cells in fibromyalgia, a study was published in the journal Scientific Reports.

Though microglia has been long suspected to be implicated with fibromyalgia, it has been difficult to study or prove this concept. But with improvement in understanding of cellular biology, it has become possible to create human-induced microglia-like (iMG) cells from other cells derived from the peripheral blood circulation.

In the published study, scientists created iMG from 14 patients suffering from fibromyalgia 10 from subjects in good health.  They studied the reactions of the iMG cells to the stimulation by extracellular ATP. Researchers found that the cells of patients suffering from FM demonstrated the higher levels of tumor necrosis factor (TNF), α kind of inflammatory messenger-cytokine. 

Result

This experiment proved the hyper-reactivity of the microglia in individuals suffering from FM. It is these hypersensitive cells that may quite possibly be responsible for the higher perception of pain, and inclination towards the mood disorders in FM.

References

Wilbarger JL, Cook DB. Multisensory Hypersensitivity in Women With Fibromyalgia: Implications for Well Being and Intervention. Arch Phys Med Rehabil. 2011 Apr;92(4):653–

American Pain Society. Fibromyalgia has central nervous system origins. ScienceDaily [Internet]. 2015 May 17 [cited 2017 Oct 21]; Available from: https://www.sciencedaily.com/releases/2015/05/150517071813.htm

McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev. 1995 Sep;21(2):195–218.

Maier SF, Watkins LR. Consequences of the Inflamed Brain [Internet]. 2012 [cited 2017 Oct 21]. Available from: http://www.dana.org/Publications/ReportOnProgress/Consequences_of_the_Inflamed_Brain/

Ohgidani M, Kato TA, Hosoi M, Tsuda M, Hayakawa K, Hayaki C, et al. Fibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells. Sci Rep. 2017 Sep 19;7(1):11882.