Investigation on developing novel biomarkers and treatments in the patients with fibromyalgia

Fibromyalgia, presenting as widespread pain, sleep problems and impaired daytime functioning, can cause long term disability and impaired quality of life. The pathomechanism for fibromyalgia is still not well-known. Fibromyalgia is considered to be as a human model disease of central sensitization. Neuro-endocrine, autonomic and neuro-image abnormality are demonstrated in recent studies. Lower serotonin and higher substance P level was found in serum and CSF in the patients with fibromyalgia. Altered circadian markers was also reported in patients with fibromyalgia. Fibromyalgia patients also have abnormal autonomic responses to stress and exercise which may be associated to its symptoms. Regional-specific abnormality in CNS was demonstrated in the functional image study in patients with fibromyalgia. However, most of data were obtained from cross-sectional studies. Therefore, there is still no known biomarker which can be applied in diagnosis, classification, guiding treatment and predicting prognosis. In present project, we aim to explore a multi-dimensional evaluation and evaluate several potential biomarkers including neurotransmitters (serotonin, substance P) , circadian markers (PER/CRY/cortisol/circadian gene), autonomic parameters (heart rate complexity), and exercise physiological parameters (exercise capacity, EEG responses during exercise) with a longitudinal study. These data can aid us to determine the correlation between the pattern of clinical symptoms and the biomarkers in fibromyalgia. Pharmacological and non-pharmacological approaches including physical modality, hydrotherapy, exercise and cognition behavior therapy play some roles in managing the patients with fibromyalgia. Nevertheless, the treatment for fibromyalgia is still a very challenging topic.We aim to investigate two novel treatments in fibromyalgia: transcranial direct current stimulation (tDCS) and virtual reality (VR) assisted exercise. tDCS can change the excitability of regional cortex. tDCS has been applied in clinical conditions such as depression, insomnia, anxiety, stroke and pain disorders and showed its positive effects. Similarly, recent developing model of VR assisted exercise demonstrated its ability in managing pain patients. However, few studies reported treating fibromyalgia by applying tDCS and VR assisted exercise in these patients. Furthermore, the effects in physiological changes following applying tDCS and VR assisted exercise in fibromyalgia are also unknown. We propose that applying tDCS and VR assisted exercise could be effective to improve the symptoms in patients with fibromyalgia.We will exam our hypothesis by a series of prospective double-blinded control trials in the third and fourth-year project. The series of studies in this project can eventually help us to exam the effectiveness and understand the pathomechanism of these novel tools in treating fibromyalgia. These data can also provide important evidence for further applications of these tools in clinical treatment of fibromyalgia