Relationship Between Sleep and Fibromyalgia

I just did a little exercise for myself and I want to share the results, and then share a new way of looking at the relationship between sleep and fibromyalgia. The exercise was to ask, “if I wanted to learn about the current thinking about fibromyalgia in the scientific and medical community, where would I look?” What field of study would be the best source of information about fibromyalgia? I don’t know much about fibromyalgia other than it has something to do with chronic pain. Because of the association with pain, I figured Neurology would be a good place to start. So I went to one of my favorite sources, Nature Reviews Neurology. I did find a few references, but I was also directed to Nature Reviews Rheumatology, which I would not have expected. My point is this. Conditions like fibromyalgia are very complex, and many times, controversial. The information you need might not be found in the most obvious places, but you have to know when to keep digging and where to dig in order to find the information you need.

Illustration of a nerve cell
Photo: Illustration of a nerve cell
Andrej Vodolazhskyi, Shutterstock

Sleep and Fibromyalgia

Fibromyalgia is a disease or condition characterized by chronic pain. Fibromyalgia sufferers have increased sensitivity to pain such that pain sensation may be triggered by stimuli that don’t normally cause pain. Light touch or even simple movements can cause the person to feel pain. To make matters worse, the diagnosis of fibromyalgia is not completely accepted within the medical community, kind of like adding insult to injury. As you might imagine, fibromyalgia suffereers are pretty miserable and often depressed. Many fibromyalgia sufferers have difficulty sleeping which exacerbates the feelings of exhaustion, pain, and depression.

New Development

Here’s the kicker–the new development. The association between fibromyalgia and sleep has been known for a long time. It has been assumed that suffering from fibromyalgia resulted in a disruption of normal sleep. Now it turns that we might have had this backward. Some investigators now believe that sleep disruption, or insomnia, may be one of the triggers of fibromyalgia, not the other way around. I know from personal experience that not being able to sleep is very serious and can lead to a variety of real and psychosomatic physical consequences. It is not surprising to me that some people could experience chronic pain sensations as a result of prolonged sleep deprivation and the anxiety that accompanies it. If you read this post, and you know someone who suffers from fibromyalgia, find out if they are able to sleep. Find out if they started having trouble sleeping BEFORE they began to suffer from fibromyalgia. This might provide some additional treatment options to explore, if you haven’t explored this possibility already.

Reference

Choy EH. 2015. The role of sleep in pain and fibromyalgia. Nat Rev Rheumatol. 2015 Apr 28. doi: 10.1038/nrrheum.2015.56. [Epub ahead of print]

Dr. Choy is in the Section of Rheumatology, Institute of Infection and Immunity, Cardiff University School of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.

Immunotherapy for Rheumatoid Arthritis

Rheumatoid Arthritis is an autoimmune disease that results in pain swelling the joints. An autoimmune disease is a condition where your immune system attacks your own tissues, in this cells and tissues lining the joints. RA involves both T cells, which directly attack other cells, and B cells which produce antibodies—in this case “auto-antibodies. RA is antigen specific, meaning that certain proteins (antigens) are targeted by the immune system. Learning which proteins these are helps us combat the disease. Over 70% of RA patients (70% is a very high proportion when it comes to disease correlation) make antibodies against a group of proteins called citrullinated proteins. The two main types of antibodies are anti-citrullinated peptide antibodies (ACPA) and anti-cyclic citrullinated peptides (anti-CCP).

Preparation and delivery of Rheumavax to a patient with rhematoid arthritis.
Preparation and delivery of Rheumavax to a patient with rhematoid arthritis. Sketch, S. Anderson.

Immunotherapy is a form of treatment where cells of the immune system are used as “drugs” to treat the disease. In present study an immunotherapy preparation called “Rheumavax” was tested for safety and effects on the immune response in small group of patients. Rheumavax is prepared by drawing blood from each patient, culturing the dendritic cells with citrullinated peptides, and then injecting back into the patient. Dendritic cells are a specialized kind of cell that present antigens to T cells in order trigger an immune response. If conditions are right (or wrong) when the dendritic cells are exposed to antigen they will turn off the immune response instead of turning it on, which is what the investigators are trying to do here. The purification and preparation of the dendritic cells takes about 2 days in tissue culture. The patients were divided into three groups. One group (9 patients) got a single low dose of Rheumavax cells (1 million), a second group (9 patients) got a single high dose of Rheumavax cells (5 million), and the third group (16 patients) got no Rheumavax cells. Both doses of cells were well-tolerated.

After 1 month the patients were evaluated for the state of their arthritis symptoms and for the number of autoimmune cells they had. The results showed the patients receiving Rheumavax showed at least some clinical improvement, which correlated with a decrease in active autoimmune T cells in their bodies. Reduced T cell responses were observed in both the low dose and high dose patient groups. This is exactly what the investigators had hoped for.

Even though this trial was a small one, with a simple design and outcome measurements, the results are very promising and suggest that this kind of immunotherapy with dendritic cells is worth pursuing in future trials.

Immunotherapy like this represents one form of so-called “personalized medicine” in which each individual patient is treated with a tailored therapy regimen based on their own physiology and disease conditions.

Reference

Benham H, Nel HJ, Law SC, Mehdi AM, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, G Brunck ME, Hyde C, Trouw LA, Dudek NL, Purcell AW, O’Sullivan BJ, Connolly JE, Paul SK, Lê Cao KA, and Thomas R. 2015. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med. Jun 3;7(290):290ra87. doi: 10.1126/scitranslmed.aaa9301.

University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.

Blood Cell Primer

This post contains some fun facts about the cells found in our blood. It’s presented in a slightly disorganized way—part table and part text. All the information comes from Wikipedia or MedLine. I hope you will find it interesting and informative. This post illustrates a couple of other points  I would like to make. All of this information is very basic and very easy to find—if you (1) know what to look for, (2) know when you’ve found the right (accurate) information, (3) know what the information means, and (4) understand how you can use it.

Composition of Whole Blood
Composition of Whole Blood centrifuged to show volume of plasma, WBCs, and RBCs (Hematocrit). Wiki Commons.

Total blood volume in an adult human: 5 Liters = 5,000 mL = 5.25 quarts = 10.5 pints.

1 Unit of blood is 500 mL = 0.5 qt, = 1 pint, about 10% of your total blood volume.

Red Blood Cells (RBCs, Erythrocytes): 4,000–6,000 x106 (106 =1 million) per milliliter (mL)

Photo of RBCs and platelets
Photomicrograph of RBCs also showing platelets. Photo: UCSF School of Medicine

 

Platelets: 150–400 x106 per mL

White Blood Cells (WBC, Leukocytes): 4.0–11.0 x106/mL

About 40-45% of your total blood volume is RBCs. That number is your Hematocrit.

There are 5 major types of WBCs. They are named for either their morphology (physical appearance under the microscope), or where they were first found. The ratio of these cells to each other is called the Differential Count, or “Diff”.

Micrograph of Neutrophils.
Micrograph of Neutrophils. Wiki Commons.

Neutrophils: 40%–60% of all WBCs in the blood

Micrograph of monocytes.
Micrograph of monocytes. Wiki Commons

Lymphocytes: 20%–40%

Monocytes: 2%–8%

Micrograph of an eosinophil.
   Micrograph of an eosinophil. Wiki Commons.
Micrograph of a basophil.
Micrograph of a basophil. Wiki Commons.

Eosinophils: 1%–4%

Basophils: 0.5%–1%

Interestingly, WBCs in the blood are only about 0.1% of all the WBCs in the body. The body has approximately 1×1012 total WBCs. The remainder are found in the lymphatic system, including the lymph nodes, and dispersed throughout our tissues, especially in the gut, liver, spleen, and skin.

Micrograph of a lymphocyte.
  Micrograph of a lymphocyte. Wiki Commons.
Scanning electron micrograph of a lymphocyt
  Scanning electron micrograph of a lymphocyte. Wiki Commons.
Transmission electron micrograph of a lymphocyte.
Transmission electron micrograph of a lymphocyte. Photo: UCSF School of Medicine.

 

Each WBC has a specific job to do.

Neutrophils, the most abundant WBCs, are our first line of defense against bacteria and other foreign invaders, especially those that enter the body through cuts, scrapes, and other injuries.

Monocytes are phagocytic cells that eat dead cells, debris, bacteria, and foreign substances. Together with another type of cell called Dendritic Cells, they alert helper T cells (below) that they need to jump into action.

Eosinophils are a primary attacker of parasites and worms.

Basophils release histamine when they are activated. When they are over-stimulated, like when you have an allergic reaction, they are the culprits. It’s a good thing we don’t have more of them, huh?

Platelets are actually small cell fragments. They are activated in response to tissue injury. When they are activated they become sticky and become trapped in webs of fibrin to form what we call clots. Platelets are also activated by fatty plaques that form in your arteries which leads to atherosclerosis. Not good.

Lymphocytes. All lymphocytes look relatively the same under the microscope, but with special techniques and technology such as flow cytometry we now know that there are several different kinds of lymphocytes with highly specialized functions.

There are CD4 T lymphocytes (CD4 T cells) also called T helper cells, and CD8 T cells called cytotoxic T cells or CTLs. CD8 T cells attack and kill other cells like cancer cells and virus-infected cells. T helper cells are necessary to initiate and support the function of other lymphocytes. As you may know, HIV, the AIDS virus, specifically infects and kills CD4 T cells, thus taking down your immune system and leaving you essentially defenseless. Those suffering from AIDS often die from a variety of unusual infections and/or cancer.

B lymphocytes or B cells, when activated by antigens and helper T cells, become plasma cells, which are the cells that make antibodies. If you have no B cells, you will have no antibodies.

Natural Killer cells. There is another type of lymphocyte that is close to being a T cell, but is not quite the same. They are called Natural Killer cells, or NK cells. NK cells circulate through the body looking for bad cells to kill. They are one of our primary defense mechanisms against cancer.

There are even more sub-types of T cells, B cells, and monocytes that I will not describe here. Just know that the immune system is highly specialized, and highly complex.

References

Wikipedia: look up each cell type by name

MedlinePlus: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm

Photo Credits

Hematocrit

By MesserWoland [GFDL (http://www.gnu.org/copyleft/fdl.html), CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/) or CC BY-SA 2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/2.5-2.0-1.0)], via Wikimedia Commons

SEM Lymphocyte

By Unknown photographer/artist (False color modifications made by myself–DO11.10) (Dr. Triche National Cancer Institute) [Public domain], via Wikimedia Commons

Lymphocyte (sang humain, normal). Coloration de May-Gründwald Giemsa, Gc = 1000. Février 2006.

TEM Lymphocyte

UCSF School of Medicine Prologue Histology Resource

http://missinglink.ucsf.edu/lm/ids_101_histo_resource/blood_cells.htm

RBCs

UCSF School of Medicine Prologue Histology Resource

http://missinglink.ucsf.edu/lm/ids_101_histo_resource/blood_cells.htm

Monocytes

By Dr Graham Beards [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Neutrophils

By Dr Graham Beards (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

Eosinophil

By Bobjgalindo (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons

Basophil

By User CS99 at German Wikipedia (German Wikipedia) [Public domain], via Wikimedia Commons