Understanding the Pathophysiology of Fibromyalgia

The human brain
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Anyone with fibromyalgia (FM) knows it causes widespread chronic pain, but the "why" behind this pain remains murky. And while the pain certainly exists, FM doesn't cause the inflammation or damage you expect of pain conditions.

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 condition characterized by central sensitization, which is a type of altered pain processing.

Altered Central Pain Processing

Central sensitization means your central nervous system, which comprises your brain and spinal cord, processes pain differently (more "sensitively") that a healthy one.

For example, people with FM interpret stimuli, like heat or pressure, as painful at lower levels than people without the condition. You also perceive these sensations as more painful (a greater intensity) than those without FM.

Several mechanisms support this idea of abnormal pain processing in fibromyalgia, including:

  • Faulty blocking of pain signals
  • Change in opioid receptors
  • Increase in substance P
  • More activity in pain-related brain regions
  • Abnormal connections between pain and emotion

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 or inhibit the further transmission of pain signals. But in people with FM, this pain-blocking system is faulty.

On top of this lack of pain inhibiting signals is an inability to block out repetitive stimuli, even if they're not painful.

For instance, a healthy person can tune out the persistent, non-painful tapping of a pencil on their hand, but with FM, you keep feeling it. This suggests an inability to filter out irrelevant sensory information from the environment. 

Change in Opioid Receptors

Research has uncovered a reduced number of opioid receptors in the brains of people with FM. Opioid receptors are the docking sites where endorphins bind so you can reap their benefits.

Because you have fewer available receptors, your brain is less sensitive to endorphins, as well as opioid painkillers like Vicodin (hydrocodone/acetaminophen) 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-Related Brain Regions

Sophisticated brain imaging tests, like functional magnetic resonance imaging (fMRI), have shown that fibromyalgia is associated with higher-than-normal activity in 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.

Abnormal Connection Between Pain and Emotion

A small study in the journal Pain, which consisted of 16 people with fibromyalgia and 16 healthy participants, applied painful stimuli to the hand while showing people pictures of things that should make them feel better.

The people without FM had a reduction in pain perception while viewing the pictures, but those with FM did not. This suggests an abnormal connection, in the brain, between pain perception and emotion.

Causes of Altered Pain Processing

Experts suspect fibromyalgia is a disorder of abnormal pain processing and believe interactions between your genes and one or more environmental factors trigger central sensitization.

That, then, is what promotes the development of FM and/or other central-pain conditions like migraines or irritable bowel syndrome.


There's 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.

If they're successful, it could eventually help researchers create specific targeted treatments for FM and possibly allow them to determine who's at risk.

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, including:

  • Poor sleep quality
  • Potential hormone disturbances
  • Peripheral pain problems (e.g., myofascial trigger points, osteoarthritis) that initiate or contribute to chronic pain

A Word From Verywell

If you have 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 system 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, therapies exist to soothe your pain and improve your quality of life. Don't suffer in silence. Reach out to your healthcare provider and to people who understand what you're going through.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Adrienne Dellwo
Adrienne Dellwo is an experienced journalist who was diagnosed with fibromyalgia and has written extensively on the topic.