Understanding the Pathophysiology of Fibromyalgia

The human brain
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We know that fibromyalgia (FM) causes widespread, chronic muscle pain, but the "why" behind this pain is unknown. Even more confusing, while the pain certainly exists, the muscles of those with FM are normal, with no evidence of inflammation or damage. Of course, pain without visible damage is hard to understand and treat, which is why for many years, fibromyalgia was erroneously deemed a psychological disease.

Over the years, though, as researchers dug deeper into the physiology of FM, they discovered that fibromyalgia is a chronic pain disorder characterized by central sensitization or altered pain processing.

Altered "Central" Pain Processing

Central sensitization means that your central nervous system, which is comprised of your brain and spinal cord, processes pain differently (more "sensitively"). For example, people with FM interpret painful stimuli, like heat or pressure, as painful at lower levels than people without the condition. They also perceive these sensations as more painful (a greater intensity) than those without FM.

There are several mechanisms to support this idea of abnormal pain processing in fibromyalgia. Here are just a few:

Faulty Blocking of Pain Signals

In healthy people, once a painful stimulus is felt, the brain signals the release of endorphins (your "natural opioids" or "feel-good chemicals"), which block the further transmission of pain signals. But in people with FM, this pain-blocking system is faulty.

With this faulty system, not only is there a lack of "pain inhibiting" signals, but there is an inability to block out repetitive non-painful sensory stimuli. For instance, a healthy person would tune out the persistent, non-painful tapping of a pencil on the hand, while a person with FM would continue to feel the tapping. This suggests an inability to filter out irrelevant sensory information from the environment. 

Change in Opioid Receptors

Changes in the numbers of opioid receptors have been reported in people with FM, specifically a reduction in the number found in the brain. Your opioid receptors are the docking sites where endorphins bind. With this reduction, a person's brain is less sensitive to endorphins, as well as opiate painkillers like Vicodin (hydrocodone/paracetamol) and Percocet (oxycodone/acetaminophen).

Increase in Substance P

People with FM have been found to have elevated levels of substance P in their cerebrospinal fluid (the clear fluid that bathes your spinal cord). Substance P is a chemical released when a painful stimulus is detected by your nerve cells. More specifically, substance P is involved with the pain threshold, which is the point at which a sensation becomes painful. Elevated levels of substance P could help explain why the pain threshold is low in people with fibromyalgia.

More Activity in Pain Sensitive Areas of the Brain

Sophisticated brain imaging tests, like the functional magnetic resonance (fMRI), demonstrate that, in fibromyalgia, activity is higher than normal in the areas of the brain that deal with pain. This suggests that pain signals are bombarding the brain or that the brain is abnormally processing pain signals from the body.

Lack of Pain Reduction With Positive Emotional Pictures

A small study in the journal Pain, which consisted of 16 people with fibromyalgia and 16 healthy participants, found that, unlike the healthy participants, the participants with FM did not show a reduction in pain when undergoing painful stimuli to the hand, along with viewing positive effect pictures. This suggests an abnormal connection between pain perception and emotion.

Causes of Altered Pain Processing

Experts suspect fibromyalgia is a disorder of abnormal pain processing and believe that an interaction between a person's genes and one or more environmental exposures triggers central sensitization. That, then, is what promotes the development of FM and/or other "central" pain disorders like migraines or irritable bowel syndrome.


In terms of genes, there is no known "fibromyalgia gene" (or set of genes) to test for at this time, but scientists are working hard to find genes involved in the pain processing pathways that are linked to fibromyalgia. This can eventually help experts create specific targeted treatments for FM.

Environmental Triggers

It's unclear what environmental exposures are connected to FM. It's possible that an infection, like a viral illness or Lyme disease, or emotional or physical trauma is what leads to the development of FM in genetically susceptible people.

Other Explanations

Keep in mind, while an altered "central" process seems to be at the heart of fibromyalgia, other factors are believed to contribute to the pain of FM like poor sleep quality, potential hormone disturbances, and peripheral pain problems, such as myofascial trigger points or osteoarthritis, that initiate or contribute to chronic pain.

A Word From Verywell

If you (or a loved one) has fibromyalgia, rest assured that your physical pain and higher sensitivity to pain is real. It's not in your mind, but rather a consequence of how your central nervous processes pain.

As experts continue to uncover and understand the biology of fibromyalgia and how it develops, be at ease knowing that you are not alone. Even more, there are therapies to soothe your pain and improve your quality of life. Don't suffer in silence. Reach out to others like you and to your doctor.

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