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Translational Research Reveals Pathophysiological Mechanism Linking Repeated Psychological Stress and Fibromyalgia Development

Researchers from Academia Sinica and Kaohsiung Medical University in Taiwan identify a pathophysiological mechanism linking repeated psychological stress with fibromyalgia, in an investigation that connects psychological pressure with physical disorders and chronic pain.

For a state of mind that many of us are familiar with, surprisingly little is understood about the physical effects of long-term psychological stress. Researchers from the Institute of Biomedical Sciences, Academia Sinica and Kaohsiung Medical University in Taiwan have discovered that repeated exposure to psychological stress is linked to stress-related pain mechanisms and levels of a clinical biomarker for fibromyalgia, in a study that is published in Annals of the Rheumatic Diseases.

Psychological stress can be caused by both external and internal factors, known as stressors, which are usually events or stimuli that lead to stress. Prolonged, repeated or severe stress is known to cause sleep disruption, cardiovascular disease, and psychological disorders. However, the physical effects of stress are not very well understood, with links to several health conditions being hypothesised but not being well established.

A team of researchers led by Dr Chen Chih-Cheng from the Institute of Biomedical Sciences, Academia Sinica and Dr Hung Chih-Hsien in Kaohsiung Medical University in Taiwan identified a pathophysiological mechanism that could lead to fibromyalgia in response to repeated and intermittent exposure to psychological stressors.

Fibromyalgia, which is also known as fibromyalgia syndrome (FMS), is characterised by chronic widespread pain all over the body in musculoskeletal tissues, with accompanying symptoms of fatigue and impairment of sleep, memory and mood. Fibromyalgia is associated with the development of other conditions, such as irritable bowel syndrome, interstitial cystitis or painful bladder syndrome, and anxiety and depression. Although it is a relatively common condition, there is currently no known cure for fibromyalgia, and treatment is currently centred around alleviating individual symptoms. The mechanisms behind fibromyalgia development are not fully understood, although some genetic factors, infections and stress events may predispose individuals to the condition.

To investigate the effects of repeated psychological stress and its potential link to fibromyalgia development, the researchers administered psychological stressors to mice using non-painful sound stimuli. The mice displayed long-lasting non-inflammatory pain behaviour, as well as fatigue and anxiety – symptoms that are in line with fibromyalgia.

The pathophysiological mechanism observed by the researchers could provide an explanation for the link between repeated psychological stress and fibromyalgia development. They found that repeated psychological stress leads to increased oxidative stress, which causes lipid oxidisation and increased levels of lysophosphatidylcholine (LPC) 16:0. Excessive levels of LPC16:0 lead to the activation of cell signalling pathways that eventually cause chronic hypersensitivity. Fibromyalgia is believed to be caused by dysregulation of pain processing pathways in the brain and spinal cord and thus the amplification of pain sensations, so this pathophysiological mechanism that results in chronic hypersensitivity could explain how disease development occurs.

The researchers further validated their findings through clinical lipidomic profiling of blood samples from fibromyalgia patients, who were found to undergo increased oxidative stress and exhibit higher LPC16:0 expression, which were correlated with more pain symptoms and fibromyalgia severity. They also investigated potential treatment methods for fibromyalgia, by reducing LPC16:0 synthesis in mice using darapladib, which is an inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2). Treatment with darapladib successfully reduced stress-induced hypersensitivity, indicating that darapladib could be useful in the treatment of fibromyalgia.

The pathophysiological mechanism investigated by researchers in this study provide new understanding of the biological basis for the links between psychological stress and physical conditions, in this case fibromyalgia, and provide potential targets for therapeutic intervention. [APBN]