Psychological stress triggers physical pain – Probing pathophysiology of fibromyalgia with translational research
As is well known, psychological stress can result in psychiatric disorders, such as depression and anxiety. But do you know that repeated exposure to psychological stress can also cause chronic physical pain? Dr. Chih-Cheng Chen, research fellow in the Institute of Biomedical Sciences, Academia Sinica (Taiwan) and Dr. Chih-Hsien Hung in Kaohsiung Medical University formed an interdisciplinary team of translational research and discovered the stress-related pain mechanism and clinical biomarker for fibromyalgia. The study results have been published in Annals of the Rheumatic Diseases.
What is fibromyalgia? What is its relationship with stress?
Fibromyalgia is a very common but mysterious pain disorder. The prevalence is up to 2~6 % of the general adult population, and fibromyalgia is one of the most common pain disorders in neurology and pain clinics. This illness is characterized by chronic widespread muscular pain. Fatigue, anxiety and depression are the common comorbidities. These symptoms can markedly affect patients’ quality of life, and even lead to disability. Mounting evidence of clinical observational studies suggests that daily psychological stressors trigger or aggravate pain in fibromyalgia. However, the causation of stress and disease development remains poorly defined by clinical investigations. Also, the underlying mechanism remains largely unknown. Unlike other inflammatory musculoskeletal disorders, fibromyalgia does not involve tissue injury or inflammation. Thus, laboratory tests in these patients commonly show non-specific findings. Accordingly, patients with this pain disorder may fail to have a definite diagnosis despite intensive examination. So far, diagnostic biomarkers for fibromyalgia are unknown, and its diagnosis mainly relies on clinical symptoms and excluding other possible causes. Also, current therapeutic approaches focus on symptomatic relief rather than curative treatment.
The discovery of stress-related pain mechanism and clinical biomarker for fibromyalgia
With the support of brain science project from Ministry of Science and Technology in Taiwan (MOST), neuroscientist Chih-Cheng Chen in Academia Sinica (Taiwan) and neurologist Chih-Hsien Hung in Kaohsiung Medical University formed an interdisciplinary team of translational research to tackle fibromyalgia. By establishing a novel translational model and investigating its mechanism, Dr. Hung and colleagues identified a possible pathophysiological mechanism of fibromyalgia. Using non-painful sound stimuli as psychological stressors, the group found that repeated and intermittent exposure to psychological stressors triggered long lasting non-inflammatory pain behaviors in mice. The stressed mice also had fatigue and anxiety-like behaviors, as observed in clinical conditions of fibromyalgia.
Additionally, the study found that repeated psychological stress induced excessive oxidative stress in animals, which thus caused lipid oxidization and subsequent upregulation of lysophosphatidylcholine (LPC) 16:0. Excessive LPC16:0 actives acid-sensing ion channel 3 on the muscle tissue to trigger nociceptive signaling and cause chronic hypersensitivity. Excessive oxidative stress and LPC16:0 expression was observed in the translational model and also in clinical investigation of fibromyalgia. Clinical lipidomic profiling of blood samples showed excessive LPC16:0 expression in fibromyalgia cases, and LPC16:0 expression was correlated with pain symptoms in patients with high oxidative stress and disease severity. Furthermore, darapladib (a platelet-activating factor-acetylhydrolase inhibitor; previously designed for anti-atherogenic purposes) effectively alleviated the stress-induced hypersensitivity by inhibiting LPC16:0 synthesis in mice, which might guide a new therapeutic approach for fibromyalgia. The study results have been published in Annals of the Rheumatic Diseases (epub ahead of print, 2020).
Dr. Chih-Cheng Chen, deputy director of Institute of Biomedical Sciences of Academia Sinica at Taipei, Taiwan.
Article link (Annals of the Rheumatic Diseases)