Epigenetic changes linked to chronic widespread pain

New research showing a link between epigenetic changes and chronic widespread musculoskeletal pain could pave the way for a better understanding of the mechanisms underlying fibromyalgia, say researchers from King’s College London.

While other research looking at metabolites in the blood shows promise in terms of developing a diagnostic blood test for the condition, one of the researchers Dr Frances Williams from the Department of Twin Research and Genetic Epidemiology told the limbic.

In the first of the epigenome analyses, identical twins were used to investigate whether DNA methylation patterns differ at specific sites in the genome in people with and without chronic widespread musculoskeletal pain.

The results published last November in PLOS ONE  identified three genes that had significant differences in the patterns of DNA methylation.

The follow on study, led by Dr Gregory Livshits at King’s College, uses a different technology that takes a much more broad sweep across the whole genome instead of targeting on a chip-based technology like the first. The results are due to be published in Pain within the next few months.

Dr Williams says the findings from both studies are interesting because they show epigenetic changes in pathways that are associated with the central nervous system.

“In the new paper again we’re finding the same things. The signal isn’t strong enough to say definitively this gene has its epigenome changed in chronic pain but what we’re seeing if we look at all of the genes as a pattern is a preponderance of genes in the central nervous system being affected,” she said.

“This plays into what we’re finding in clinical trials where the drugs that are used currently work fairly centrally. And other therapies like cognitive behavioural therapy which has been shown to be really useful in this condition is again acting on the central nervous system. So increasingly we’re thinking that is going to be the place where the biggest differences are found.”

Dr Williams believes there will be a lot more studies using similar designs in the next few years, but says that for now the tools limit what can be achieved.

“The tools are picking up very subtle signals and so it’s very difficult to show statistically that you have a major effect. I think what we’re waiting for is an improvement in the technology before we can really use it to crack this nut.”

In the meantime, she believes a diagnostic test for fibromyalgia is more likely to come from metabolites research and has already published these results suggesting abnormalities in steroid hormone pathways.

“Recently, we’ve got really exciting results looking at blood metabolites,” Dr Williams added.

“If we collect together a panel of about fifteen different metabolites we get a really quite nice predictive test that shows people with chronic widespread pain are susceptible to fatigue as part of their illness.

“We don’t fully understand what these metabolites are doing, but we can show that they’re very highly linked to the presence of having fatigue.”

These results should be published mid-year.

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