Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction

Although coenzyme Q10 (CoQ10) supplementation has shown to reduce pain levels in chronic pain, the effects of CoQ10 supplementation on pain, anxiety, brain activity, mitochondrial oxidative stress, antioxidants, and inflammation in pregabalin-treated fibromyalgia (FM) patients have not clearly elucidated. We hypothesised that CoQ10 supplementation reduced pain better than pregabalin alone via reducing brain activity, mitochondrial oxidative stress, inflammation, and increasing antioxidant levels in pregabalin-treated FM patients. A double-blind randomised placebo-controlled trial was conducted. Eleven FM patients were enrolled with 2 weeks wash-out then randomly allocated to 2 treatment groups; pregabalin with CoQ10 or pregabalin with placebo for 40 d. Then, patients in CoQ10 group were switched to placebo, and patients in placebo group were switched to CoQ10 for another 40 d. Pain pressure threshold (PPT), FM questionnaire, anxiety, and pain score were examined. Peripheral blood mononuclear cells (PBMCs) were isolated to investigate mitochondrial oxidative stress and inflammation at day 0, 40, and 80. The level of antioxidants and brain positron emission tomography (PET) scan were also determined at these time points. Pregabalin alone reduced pain and anxiety via decreasing brain activity compared with their baseline. However, it did not affect mitochondrial oxidative stress and inflammation. Supplementation with CoQ10 effectively reduced greater pain, anxiety and brain activity, mitochondrial oxidative stress, and inflammation. CoQ10 also increased a reduced glutathione levels and superoxide dismutase (SOD) levels in FM patients. These findings provide new evidence that CoQ10 supplementation provides further benefit for relieving pain sensation in pregabalin-treated FM patients, possibly via improving mitochondrial function, reducing inflammation, and decreasing brain activity.     

Effectiveness of cognitive behaviour therapy for the treatment of catastrophisation in patients with fibromyalgia: a randomised controlled trial

Introduction  

No randomised, controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising (PC) in patients with fibromyalgia. Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy (CBT) and the recommended pharmacological treatment (RPT) compared with treatment as usual (TAU) at the primary care level for the treatment of PC in fibromyalgia patients.     

Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation

Abstract

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n = 10) and in healthy control subjects (n = 67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.     

Stress and psychophysiological dysregulation in patients with fibromyalgia syndrome

Fibromyalgia syndrome (FMS) is a prevalent musculoskeletal pain disorder characterized by diffuse pain and associated psychophysiological symptoms. Despite extensive research in the past 3 decades, the etiology and pathophysiology of FMS and effective treatment approaches are yet to be delineated. Recently, it has been suggested that FMS may be related to hypofunctional stress systems, particularly in the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Studies have demonstrated that patients with FMS exhibit lowered sympathoadrenal reactivity to stress. These findings seem to be consistent with the large volume of research indicating the inverse relationship between pain sensitivity and sympathetic reactivity. In this paper, we discuss the role of stress in the pain experience in general, stress in patients with FMS, and review the studies evaluating the ANS and HPA functions in response to various stressors.     

Evaluation of Psychophysiological Asymmetry in Patients with Fibromyalgia Syndrome

Fibromyalgia syndrome (FMS) is characterized by systemic pain of unknown etiology, and is often accompanied by various psychological symptoms. In the present study, differences in surface electromyographic (SEMG) levels of the trapezius muscle, skin temperature (TEMP) and skin conductance level (SCL) were compared between the right and left side of the body in 31 FMS and 47 control subjects (Control Group). We observed significant asymmetries of SEMG level, TEMP and SCL in the FMS Group. These asymmetries might be related to central, peripheral and autonomic nervous system dysfunctions. Marked increase of SEMG levels, and a decrease of TEMP and SCL were observed at the dominant side in the FMS Group, and a negative correlation of SEMG levels with TEMP and SCL was found. These results suggest that continued antalgic postures in response to pain at the dominant side in FMS patients might lead to asymmetries of SEMG level, TEMP and SCL. Thus, a focus on pain related behaviors and muscle asymmetry might be a useful therapeutic approach.     

Altered near‐infrared spectroscopy response to breath‐holding in patients with fibromyalgia

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain and a heightened response to pressure. Most medical researches pointed out that FM patients with endothelial dysfunction and arterial stiffness. A continuous‐wave near‐infrared spectroscopy (NIRS) system is used in present study to measure the hemodynamic changes elicited by breath‐holding task in patients with FM. Each patient completed a questionnaire survey including demographics, characteristics of body pain, associated symptoms, headache profiles and Hospital Anxiety and Depression Scale. A total of 27 FM patients and 26 health controls were enrolled. In comparison with healthy controls, patients with FM showed lower maximal and averaged change of oxyhemoglobin concentration in both the left (1.634 ±0.890 and 0.810 ±0.525 μM) and the right (1.576 ±0.897 and 0.811 ±0.601 μM) prefrontal cortex than healthy controls (P < .05 for both sides) during the breath‐holding task. In conclusion, FM is associated with altered cerebrovascular reactivity measured by NIRS and breath‐holding task, which may reflect endothelial dysfunction or arterial stiffness. Oxygenated hemoglobin concentration changes of healthy controls and FM patients.      

Levels of lipid peroxidation,nitric oxide,and antioxidant vitamins in plasma of patients with fibromyalgia

The etiology of fibromyalgia is not clearly understood. In recent years, a few studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of fibromyalgia. The aim of this study was to investigate plasma antioxidant vitamins, lipid peroxidation (LP), and nitric oxide (NO) levels in patients with fibromyalgia and controls. The study was performed on the blood plasma of 30 female patients and 30 age‐matched controls. After a fast of 12 h, blood samples were taken, and plasma samples were obtained for measurement of vitamins A, C, E, and β‐carotene concentrations and levels of LP and NO. Concentrations of vitamins A (p < 0.01) and E (p < 0.001) were significantly lower in patients with fibromyalgia than in controls, and LP levels were significantly (p < 0.05) higher in the plasma of the patients than in controls. Concentrations of vitamin C and β‐carotene and levels of NO did not change significantly. These results provide some evidence for a potential role of LP and fat‐soluble antioxidants in the patients with fibromyalgia. Copyright © 2009 John Wiley & Sons, Ltd.