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Possible Causes


How can you hurt from head to toe and have countless other symptoms, yet lab tests are normal? Fibromyalgia consists of a slew of malfunctions, most of them hidden away in the central nervous system (spinal cord and brain) or CNS. There are no signs of injury or disease, but several less conspicuous abnormalities throughout your body that may be driving your symptoms. The point is, the findings in fibromyalgia are not obvious.

The onset of fibromyalgia is believed to be triggered by an event or threat to the body (infection, injury, prolonged stress, trauma, another disease such as rheumatoid arthritis, etc.) that disrupts your pain processing system. Ordinarily, the pain circuitry quiets down once the event has resolved, but in genetically predisposed people, things go haywire and chronic widespread pain develops. In turn, the mishaps in the CNS set off a snowstorm of other symptoms.

Pain normally serves a protective role, forcing you to take it easy so that your damaged tissues or pulled muscles can heal. It’s a danger signal designed to prevent you from risking further injury. Yet the chronic pain of fibromyalgia has long outlived its purpose, resulting in a disease of the CNS as well as the peripheral systems that feed into it.

Where is Your Pain?

You may feel as though all your muscles are wrenched, but the pain does not actually occur there. Any information (signal) about possible damage to the tissues comes from the periphery. Yet, the perception of that signal as painful occurs in the brain, not the tissues.

Distinguishing between where injury or disease occurs and how pain is perceived is essential for explaining the widespread discomfort of fibromyalgia. Otherwise, if one thinks that the cause of pain must be in the tissues felt to be “painful,” one can clearly become suspicious when no injury to the tissue is found. In turn, this leads to the false assumption that your pain is of psychological origin.

To understand an abnormal pain state like fibromyalgia, you first have to know what’s considered “normal.” The next section takes you through the Cliff Notes version of what should happen if you merely stubbed your big toe.

Pain Control Simplified

Jamming your toe will hurt, but the soreness is gone in days if your pain circuitry works properly (see figure below). Chemicals are released in the injured toe, activating sensory nerve fibers that send signals to the spinal cord. After a few relay stations, the signals reach the brain where they are interpreted as pain localized to the toe.

The communication highway from the toe to the brain has checkpoints surrounded by immune cells called glia. Ordinarily, these cells nurture the neurons but they also survey he environment for any threat, such as an injury. When the toe is stubbed, the glia pour out substances that sensitize nerves so they fire off more alarm signals to get the brain’s attention. Below is the three-step process that follows a stubbed toe.

  1. The tentacle-like endings of sensory nerves pick up chemical changes in your sore toe and start generating noxious signals that travel up the leg to the spinal cord. Just before these transmissions enter the cord, they pass through a bulb-shaped structure called the dorsal root ganglia. The ganglia house the nucleus (or the brain) of each neuron that passes through it; they are located at each level of your spine on both your right and left sides. (These ganglia can decrease or increase the signal, and research indicates they may be doing the latter in people with fibromyalgia.)
  2. The noxious signals connect with neurons just inside the spinal cord. Here there are special spinal neurons that can release opioids and other pain-relieving substances to dull the pain. The glia in your CNS can morph into an activated state, causing the release of substances that temporarily sensitize the sensory neurons and bolster the signal to get the brain’s attention. (Most of the time, the glia sit quietly on the sidelines and only act up when tissue is injured or the body is threatened.)
  3. Once the signal travels up the spine to connect with the neuron/glia checkpoints in the brainstem and then the cortex, additional processes to reduce the pain and aid in the toes’ recovery are triggered.

If everything works as it should, you will protect the foot with the injured toe, and the noxious inputs to your CNS will stop. Your glia will turn mellow and nurturing again, and the pain will go away. But in fibromyalgia, the triggering event (probably more than a stubbed toe) doesn’t resolve and you are left with a chronic, painful disease. Your genetics are likely to blame.

Role of Genetics

First degree blood relatives of fibromyalgia patients are 8.5 times more likely to develop this condition. In fact, all family members have lower-than-normal pain thresholds, even if they do not present with the widespread pain of fibromyalgia. Researchers estimate that 50 percent of the risk of developing fibromyalgia is due to genetics. The other 50 percent is due to environmental triggers, such as infections, injury (especially to the spine), prolonged stress, trauma, or another disease (e.g., rheumatoid arthritis).

Genetic alterations in the body’s production of pain-relieving chemicals tend to occur more commonly in fibromyalgia. For example, researchers have found genetic differences in serotonin and dopamine production as well as changes in the way opioids work. However, each abnormality only occurs in a subset of patients and many more have yet to be determined. These genetic differences may explain the variability in symptoms, but no one culprit appears to cause fibromyalgia.

What is it about your genetic makeup that makes you more vulnerable to developing FM? A large-scale brain imaging study looked at children (9-10 years old) over a one-year period. All were pain-free to begin with, but the children who later developed pain displayed alterations in the way their brains operated. In fact, the youngsters who experienced pain in multiple regions just one year later showed similar aberrant changes in brain function to that of adults diagnosed with fibromyalgia.

Although the brain imaging study in children shows a predisposition to abnormal brain function in fibromyalgia, there are many contributing factors. The problem could be at the level of the spinal cord, the brainstem, or the brain – or a person might have defects at all three levels of processing incoming signals. In addition, the driving force of your brain malfunctions likely resides outside the CNS in one of many peripheral systems. Examples include your GI system, your immune system, and your metabolic functions.

Subtle alterations in the immune system (including components in the blood) can cause the dorsal root ganglia to ramp up the transmissions entering the cord. Over time, the CNS becomes overloaded and the brain doesn’t work properly. More than likely, these immune changes are tied to genetics as well.

Everyone thinks of the GI system as mindlessly digesting food. Not true! This system has a direct line of communication with the brain (and vice versa) and it is disrupted in fibromyalgia. Again, the GI abnormalities and other system problems are probably tied to your genetics.

So, fibromyalgia is caused by genetics in combination with environmental triggers. However, you are probably more interested in learning about the CNS and the peripheral system abnormalities that drive your symptoms. After all, you can’t change your genetics and you can’t go back in time to undo the environmental exposure. Besides, many of the deviations identified by researchers are somewhat amenable to treatment.

One more thing: when researchers report that an abnormality is more prevalent in fibromyalgia patients versus healthy people, it doesn’t mean every patient has this problem. Diffuse widespread pain is the cumulative result of different glitches in the CNS pain control and peripheral systems that feed into it. Keep this in mind because it helps explain the variable response to treatments.

One person might have an amazing response to a drug, while another may think it was worthless. Both people may have fibromyalgia, but their genetics and the processes that cause their symptoms might differ.

For simplicity, the Central Nervous System is presented first, followed by a section of articles pertaining to the Peripheral Systems. The last section on Tests/Biomarkers includes studies showing that fibromyalgia pain and other symptoms can be measured. It also describes research reports on potential biomarkers for this disease.