Psychological stress triggers physical pain – revealing the mysterious pathophysiology of fibromyalgia

Psychological stress triggers physical pain – revealing the mysterious pathophysiology of fibromyalgia

As is well known, psychosocial stress can result in psychiatric disorders, such as depression and anxiety. But do you know that psychological stress can also cause chronic physical pain?

In the current pandemic of COVID-19, psychological stress is pervasive and inevitable globally for people. Psychosocial stress can not only precipitate psychiatric illness but also various somatic pain disorders. Fibromyalgia is a very common but mysterious pain disorder, and the prevalence is up to 2~6 % of the general adult population. This illness is characterized by chronic widespread muscular pain. Fatigue, anxiety and depression are the common comorbidities. 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 pain disorders, 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. Also, current therapeutic approaches focus on symptomatic relief rather than curative treatment.

To this end, neurologist Chih-Hsien Hung in Kaohsiung Medical University hospital and neuroscientist Chih-Cheng Chen in Academia Sinica (Taiwan) 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 the Annals of the Rheumatic Diseases (December, 2020).

Graphical Abstract

Application and Highlights:

1.This research identified a plausible causative mechanism of psychological stress exposure and

fibromyalgia development.

2.The research found a possible therapeutic approach for fibromyalgia by modifying the algesic oxidized

lipid LPC16:0.

Research Team Members: Dr. Hung Chih-Hsien, Prof. Chih-Cheng Chen, Prof. Chiu-Lian Lai, Prof. Chu-Huang Chen and Dr. Ming-Hsien Tsai.

Representative Department: Department of Neurology, Kaohsiung Medical University Hospital

Introduction of Research Team: Dr. Hung is currently an attending physician of Kaohsiung Medical University Hospital. Professor Chih-Cheng Chen is deputy director of Institute of Biomedical Sciences of Academia Sinica at Taipei, Taiwan. He is also director of Taiwan Mouse Clinic.

Contact Email: jasonhung0701@gmail.com

Publication: Annals of the Rheumatic Diseases 2020 Dec;79(12):1644-1656.

Full-Text Article: Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain | Annals of the Rheumatic Diseases (bmj.com)