How Lyrica Changes the Fibromyalgia Brain

Structural & Connectivity Changes

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Lyrica (pregabalin) makes changes to brain structure and gray-matter volume in people with fibromyalgia, according to research (Piui) published in early 2016.

Lyrica was the first FDA-approved drug for fibromyalgia. It's an anti-seizure medication, but it's also been found to work against the pain of fibromyalgia, diabetic neuropathy, and surgery.

However, exactly how it does so isn't clear. This new research may help explain how Lyrica works to combat pain.


In this study, 16 women with fibromyalgia went through two trial periods of a randomized, double-blind, placebo-controlled study. Researchers examined their brains with functional magnetic resonance imaging (fMRI) before treatment began and after each trial period.

They were looking specifically at:

  • Gray-matter volume;
  • Connections between different areas while pain is caused.

The gray matter of your brain – the mass of neurons that send and receive electrical signals – naturally diminishes as we age. According to a few studies, it appears to diminish more rapidly in those with fibromyalgia than in healthy people. At the same time, some research has shown that particular areas are larger than average.

Studies have also shown abnormal activity levels in the areas of the brain that process pain, as well as abnormal connectivity between different regions, that demonstrate the severity (and very real nature) of fibromyalgia pain.

Researchers believed this to be the first ever study looking at changes in gray-matter volume and pain-evoked connectivity in people being treated with Lyrica.

The Results

After analyzing the before-and-after brain scans, researchers noted several interesting things after treatment in the Lyrica group, including:

  • Reduced gray-matter volume in an area believed to be important to pain processing – the posterior insula. The insula also deals with emotion, homeostasis, and many other things.
  • Reduced gray-matter volume in the medial frontal gyrus in participants who reported less pain. This area is linked to higher functions such as decision making.
  • A reduction in connectivity between multiple regions while pain was created through pressure. This finding also was associated with reports of reduced post-treatment pain.

Researchers concluded that short-term Lyrica treatment reduces pain by, at least in part, rapidly changing brain structure and connectivity during pain.

This study also gives us a better understanding of where "problem" areas may be in the fibromyalgia brain so that future treatments can target them.

My Lyrica Experience

I took Lyrica for a couple of months about a year after I was diagnosed with fibromyalgia. I have to say, these study results are fascinating to me because of something that happened after my first dose.

About two hours after taking the first pill, I swear I felt a physical sensation like something was moving across my brain. It was the strangest thing! Before I felt it, I was in a fair amount of pain, physically sluggish, and mentally dull.

After the odd sensation, I had very little pain and felt awake for the first time in forever. That night, I had what felt like the best sleep of my life, and I woke up refreshed. Refreshed! That's definitely not normal for me. I even took a walk after breakfast. It seemed like a miracle.

Sadly, I wasn't able to tolerate Lyrica. Severe side effects kicked in and I had to wean off of it after several weeks. However, I can't help but wonder whether I felt the changes the researchers saw, or at least something similar to them.

(When talking about treatments, always remember that we each have our own unique responses to them and that my experience may be nothing like yours. Don't assume that you'll have the same successes or failures as someone else.)

Learn More


Kuchinad A, et al. Journal of neurocience. 2007 Apr 11;27(15):4004-7. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?

Puiu T, et al. Arthritis and rheumatology. 2016 Jan 27. Alterations in gray matter volume are associated with reduced evoked-pain connectivity following acute pregabalin administration.

Schmidt-Wilcke T, et al. Pain. 007 Nov;132 Suppl 1:S109-16. Striatal gray matter increase in patients suffering from fibromyalgia—a voxel-based morphometry study.

Talati A, Hirsch J. Journal of cognitive neuroscience. 2005 Jul;17(7):981-93. Functional specialization within the medial frontal gyrus for perceptual go/no-go decisions based on "what," "when," and "where" related information: an fMRI study.

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