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Experts Review the Science of Fibromyalgia

In September 2011, fibromyalgia experts Dr Daniel Clauw, Dr Lesley Arnold and Dr Bill McCarberg published a review of the science of fibromyalgia in the Mayo Clinic Proceedings journal on behalf of the FibroCollaborative (a diverse group of leading experts on FM). It is an excellent summary designed to bring the science of fibromyalgia to the attention of clinicians and explain that: "it is no longer accurate to state the FM is 'poorly understood'."

Here is a summary of the main points covered in the review.

Fibromyalgia is a common condition, estimated to affect 2-5% of the adult population. It is a persistent and debilitating disorder that can have a devastating effect on people's lives, affecting their ability to work and engage in everyday activities, and their relationships with family and friends.

Chronic widespread pain is the major symptom in FM. This pain is caused by imbalances in certain chemicals that transmit or dampen down pain signals in the central nervous system (the spinal cord and brain), and leads to central amplification. People with FM have an increased sensitivity to pressure and touch which is not normally painful (allodynia) and an increased reaction to painful stimuli (hyperalgesia) as a result.

It is as though the volume control setting for pain is turned up too high in FM. You have pain signals coming in from different areas of the body which are amplified in the spinal cord by the abnormally high levels of chemicals namely substance P, nerve growth factor and glutamate. To make matters worse, other chemicals that normally dampen down incoming pain signals are also out of balance. These chemicals called serotonin, norepinephrine and dopamine are in lower supply than normal in FM and therefore struggle to do their job of dampening down incoming pain signals. The overall result is a high volume setting for pain leading to pressure and touch which are not normally painful, being translated as pain.

What triggers these changes in the central nervous system is not completely understood, but it's thought to almost certainly involve a combination of factors. The volume control setting for pain varies widely between different individuals in the general population. Genetic factors and environmental influences are likely to be at least partially responsible for the volume setting and for an individual’s susceptibility to developing central amplification.

Dysfunction in the central nervous system can also help to explain some of the other symptoms of FM such as sensitivity to other factors including heat, cold, sound and electrical stimuli. Other conditions including irritable bowel syndrome, temporomandibular disorder (jaw pain), chronic pelvic pain, irritable bladder syndrome and vulvodynia are also experienced by people with FM and these are likely to share the same underlying mechanism of pain amplification. Serotonin, norepinephrine and dopamine also influence mood, energy and sleep, so imbalances in these chemicals in different regions of the brain can help to explain why mood disorders, sleep dysfunction and fatigue are frequently associated with FM.

The evidence to support central amplification in FM is now quite extensive. For example, studies measuring pain thresholds have shown that people with FM perceive pain in response to pressure at a lower threshold compared with healthy volunteers. Also, studies involving imaging of the brain show that blood flow is greater in areas of the brain associated with pain processing in people with FM compared with healthy volunteers when they receive a pain stimulus.

The understanding that the chronic widespread pain in FM is due to abnormalities in the central nervous system also helps to explain why certain medications are more effective in treating FM than others. For example, nonsteroidal anti-inflammatory drugs and paracetamol act primarily in what is called the peripheral nervous system which is all the nerves that reach out to the different areas of the body rather than those concentrated in the spinal cord and brain. Therefore these medications are less effective in treating FM unless there is specific inflammation or tissue damage present. Medications such as serotonin-norepinephrine reuptake inhibitors (duloxetine, milnacipran, tricyclics and tramadol) and alpha-2-delta ligands (pregabalin and gabapentin) target the central nervous system and therefore can be more effective.

However, the symptoms of FM can vary from person to person indicating that the underlying abnormalities in the central nervous system can also vary. This means there is not one drug that will work for everyone and it is important to try more than one approach to find what works for you. Interestingly, opioid levels in people with FM are increased but the number of opioid receptors available is decreased, which may help to explain why opioids are not always effective in treating FM as the opioids have few receptors to bind to and therefore can't have much of an effect.

Other areas of research are focusing on abnormal functioning of the autonomic nervous system (a system that controls functions such as heart rate, breathing, temperature etc), activation of glial cells (cells that surround the neurones providing support and insulation and are capable of responding to various signals), grey matter loss, and hormonal abnormalities controlled by the master pituitary gland in the brain. Also, researchers are trying to identify different subsets of FM patients who respond better to one type of therapy than to others, and to see whether FM actually worsens without adequate treatment.

By Kathy Longley


Daniel J. Clauw, MD; Lesley M. Arnold, MD; and Bill H. McCarberg, MD; for the FibroCollaborative. The Science of Fibromyalgia. Mayo Clinic Proceedings September 2011; 86(9):907-911

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