Researchers currently regard the endocannabinoidome, which generally describes the endocannabinoid system, as a potential therapeutic target for chronic pain. This system is composed of lipid (fat)-based neurotransmitters known as ECs, which bind to specific receptors throughout the central nervous system.
The endocannabinoid system is part of the immune system and affects pain and inflammation. Different ECs have shown analgesic properties via activation of cannabinoid (CB) receptors 1 and 2. The endocannabinoid system also includes N-acylethanolamines (NAEs), which are lipid mediators that do not target CB receptors.
The research team from Sweden had previously described different levels of NAEs in women with chronic widespread pain, a typical manifestation in fibromyalgia, than in controls. However, the evidence on these mediators is still limited.
The scientists now analyzed plasma levels of different ECs — arachidonoylethanolamide (AEA), palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamide (SEA) and 2-arachidonoylglycerol (2-AG) — in 104 women with fibromyalgia and in 116 healthy controls.
They assessed correlations between these compounds and pain characteristics, psychological aspects, and health status, while also exploring their potential as biomarkers for fibromyalgia. All women were required to rate their pain, anxiety, depression, and current health status.
Results revealed that levels of OEA, PEA, SEA, and 2-AG were significantly higher in fibromyalgia than in healthy controls, but only OEA and SEA remained significantly different after accounting for age and body mass index (BMI).
The data also showed that the higher the concentration of 2-AG — one of the better characterized ECs — the longer the duration of fibromyalgia and the higher the BMI. However, 2-AG correlated negatively with pain, anxiety, depression, and health status.
These results of 2-AG may suggest this compound is the strongest candidate to serve as a biomarker for fibromyalgia, but the large variability in its levels indicate other factors may be better suited.
In the group with fibromyalgia, levels of AEA were higher in women with higher depression ratings. However, no differences were found between AEA levels in women with fibromyalgia compared to controls.
“The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of [fibromyalgia] and might be signs of ongoing low-grade inflammation,” the scientists wrote.
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