Possible Mechanism and Treatment for Fibromyalgia Reported

September 30, 2020

Lysophosphatidylcholine 16:0 (LPC16:0), an oxidized lipid, may mediate the pain that people with fibromyalgia experience, according to researchers writing in the Annals of the Rheumatic Diseases.

Lysophosphatidylcholine 16:0 (LPC16:0), an oxidized lipid, may mediate the pain that people with fibromyalgia experience, according to researchers writing in the Annals of the Rheumatic Diseases.

The discovery, based on studies in both mice and humans, could lead to a new treatment, such as with darapladib, an anti-inflammatory now under investigation for treatment of atherosclerosis.

“Clinical evidence showed that excessive LPC16:0 exists in fibromyalgia cases, and LPC16:0 expression was correlated with pain symptoms in patients with high oxidative stress and disease severity,” wrote Chih-Hsien Hung, of the Institute of Biomedical Sciences Academia Sinica in Taipei, Taiwan, and colleagues.

Because of its correlation to psychological conditions and absence detectable tissue damage, researchers have long considered fibromyalgia a central pain disorder related to stress.

To explore the mechanism of this stress, the researchers subjected mice to unpleasant noises, increasing them from once to six times per day. Compared to a group of mice used as controls, those subjected to the noises showed signs of anxiety, such as less weight gain and poor nesting behavior. They became hypersensitive to both touch and temperature. And their levels of plasma corticosterone and epinephrine increased.

In necropsy researchers found no signs of tissue damage. Tumor necrosis factor-alpha, intramuscular pH levels and activating transcription factor 3 didn’t differ between the stressed mice and the control mice. But the level of phosphorylated extracellular signal-regulated kinase – a marker of neuronal activation – was elevated in the stressed mice.

Since stress can causes oxidation of lipids, the researchers analyzed various oxidized lipids. They found that lysophosphatidylcholine 16:0 increased 47% when the mice were most stressed. To see if it contributes to chronic pain development they injected it into mice. Sure enough, the mice became more sensitive to pain than mice injected with an inactive substance.

On the other hand, the researchers found that they could counter the effects of the lysophosphatidylcholine 16:0 injection by administering darapladib, a selective platelet-activating factor acetylhydrolase inhibitor. Antioxidants had a similar benefit.

Next, the researchers compared 31 newly diagnosed fibromyalgia patients with 30 healthy people of the same ages and genders. The patients with fibromyalgia reported higher stress, and their stress correlated modestly with levels of lysophosphatidylcholine 16:0 as well as other metabolites.

The correlation only applied to the patients with the most severe symptoms, however. And the researchers noted that the lysophosphatidylcholine pathway may be just one of the mechanisms for the development of fibromyalgia. Still, they suggested that clinical trials of selective platelet-activating factor acetylhydrolase inhibitors are warranted.

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REFERENCE

Hung C, Lee C, Tsai M, et al. Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain. Annals of the Rheumatic Diseases Published Online First: 09 September 2020. doi: 10.1136/annrheumdis-2020-218329