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CREDIT Mart Production (Pexels).

A research team from the Universitat Rovira i Virgili, the University of Ohio and the University of Texas has developed an innovative method for reliably diagnosing fibromyalgia from a blood sample. Identifying this disease nowadays is highly complex, especially because the symptoms are similar to those of other rheumatic pathologies and persistent COVID-19. This new study represents an important step forward in the accurate diagnosis and personalisation of treatment for affected individuals, and at the same time, opens new avenues for research into this pathology and clinical care. The results of the study have been published in the journal Biomedicines.

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Fibromyalgia is a chronic disease that affects 6% of the population worldwide and is characterized by widespread muscle pain and fatigue. The variety of symptoms can easily be confused with other disorders, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis or chronic low back pain. This means that reaching a diagnosis is not easy or quick and, therefore, ends up having an impact on the quality of life and mental health of the people who suffer from it.

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To carry out the study, the research team collected blood samples from three different groups: people diagnosed with fibromyalgia, people with similar rheumatic diseases and people without any of these pathologies, who served as a control group. A combination of techniques was used to isolate and analyse specific chemical signals in the blood that could help differentiate fibromyalgia from other diseases with similar effects on health to open a more accurate and faster diagnostic pathway.

The blood samples underwent filtration, which allows the focus to be put on a very specific part of the blood that contains small molecules, known as the low molecular weight fraction. These molecules can include a variety of substances, for example, amino acids, which act as the building blocks of proteins.

To analyse these tiny molecules, the researchers used the technique of Raman spectroscopy, which consists of “illuminating” the samples with a special laser light and studying how they react. This technique makes it possible to observe which molecules are present and in what quantities based on how light interacts with them. Gold nanoparticles were used to refine this process further, increasing the signal they receive from the small molecules and making the results clearer and easier to interpret.

A statistical method classified the samples based on their chemical characteristics so that the differences between groups could be determined. The results highlighted that some patterns in small molecules, such as amino acids, could serve as “chemical signatures” to distinguish fibromyalgia from other diseases.

“This tool is fast, accurate and non-invasive, and can easily be integrated into the clinical environment to improve the quality of life of patients with fibromyalgia”, says Sílvia de Lamo, a researcher from the URV’s Chemical Engineering Department, who played a part in the research during a stay at Ohio University, where she collaborates with two research groups specialising in vibrational spectroscopy as a method for diagnosing diseases. The tool, which is still in the validation phase, could be available in health centres in about two years, according to the research team.

Fibromyalgia is common, affecting around 2% of people in the general population.1,2 The 2017 EULAR recommendations state that tramadol – a weak opioid – may be considered for pain management in fibromyalgia, but advise against use of strong opioids due to lack of evidence of efficacy, and the high risk of side effects and addiction.3 However, with limited therapeutic options available to tackle this condition, opioids are frequently used in clinical practice.

The impact of the opioid epidemic in North America has caused concern around the world. Long-term opioid use is associated with potential harm and adverse outcomes. In their abstract presented at the 2023 annual congress, in a session on Pain in RMDs, Ramirez Medina and colleagues argue that understanding the factors associated with long-term opioid use in such patients is the first step in helping to develop targeted interventions for de-prescribing.

The team conducted a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD) – a UK database of electronic health records from primary care. Overall, 28,554 fibromyalgia patients without prior cancer who were new opioid users between 2006 and 2021 were included. Long-term opioid use was defined as having at least three opioid prescriptions within a 90-day period, or at least one prescription lasting 90 days or more in the first year of follow-up.

Findings show that 26% of new opioid users became long-term users in the first year. Several factors were associated with higher risk of long-term opioid use. These included mean daily morphine milligram equivalents (MME) at initiation, history of suicide and self-harm, substance use disorder, deprivation, and obesity. Modelling showed that, of these, the three most important variables were mean MME/day at initiation, history of suicide and self-harm, and deprivation.

Fibromyalgia is common, affecting around 2% of people in the general population.1,2 The 2017 EULAR recommendations state that tramadol – a weak opioid – may be considered for pain management in fibromyalgia, but advise against use of strong opioids due to lack of evidence of efficacy, and the high risk of side effects and addiction.3 However, with limited therapeutic options available to tackle this condition, opioids are frequently used in clinical practice.

The impact of the opioid epidemic in North America has caused concern around the world. Long-term opioid use is associated with potential harm and adverse outcomes. In their abstract presented at the 2023 annual congress, in a session on Pain in RMDs, Ramirez Medina and colleagues argue that understanding the factors associated with long-term opioid use in such patients is the first step in helping to develop targeted interventions for de-prescribing.

The team conducted a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD) – a UK database of electronic health records from primary care. Overall, 28,554 fibromyalgia patients without prior cancer who were new opioid users between 2006 and 2021 were included. Long-term opioid use was defined as having at least three opioid prescriptions within a 90-day period, or at least one prescription lasting 90 days or more in the first year of follow-up.

Findings show that 26% of new opioid users became long-term users in the first year. Several factors were associated with higher risk of long-term opioid use. These included mean daily morphine milligram equivalents (MME) at initiation, history of suicide and self-harm, substance use disorder, deprivation, and obesity. Modelling showed that, of these, the three most important variables were mean MME/day at initiation, history of suicide and self-harm, and deprivation.

CAPTION

Using data from magnetic resonance imaging, the researchers were able to compare the brains of healthy and fibromyalgia sufferers.

CREDIT

© Benjamin Mosch

Changes in the pain network

The team surrounding Professor Martin Diers and Benjamin Mosch analysed the magnetic resonance imaging data of 23 female patients with fibromyalgia and 21 healthy control subjects. They wanted to examine the volume of the grey matter, i.e. the nerve cells, in various pain-processing areas of the brain, and the so-called white matter, which mainly consists of the fibre connections between the nerve cells through which signals are transmitted. “One of our goals was to find out whether the directionality of the diffusion of water molecules differs in certain areas of the brain, in other words: whether we can identify any regional differences in signal transmission,“ explains Benjamin Mosch.

The researchers found changes of the grey matter volume mainly in the pain network of the brain, i.e. in the regions responsible for processing and evaluating pain. “In certain regions responsible for the inhibition of pain, we found a decrease in grey matter in the patients compared to the healthy individuals,” explains Benjamin Mosch. “In patients, the volume of these regions was significantly reduced.”

Regarding the transmission of signals, changes were found in the thalamus. The thalamus is considered as an important node in neuronal pain processing. The deviations of the white matter in patients with fibromyalgia compared to healthy controls indicate an altered conduction of pain signals in patients with fibromyalgia.

Relationships between brain structure, perception and behaviour

The team finally related the results of the structural brain changes to perceptional and behavioural characteristics of the study participants. The amount of decreased volume in a number of relevant brain regions is inversely related with the amount of perceived pain the patients report. The researchers made an interesting observation when analysing the correlation between depressiveness or activity levels with the change in the volume of certain brain areas. The volume of the so-called putamen correlated negatively with the expression of depressive symptoms and positively with the activity level of the participants. “This indicates that changes in the brain may not be permanent, but that they can be influenced; in other words they might be reversible, for example through an active everyday life,” concludes Benjamin Mosch.