The Role of Oxidants/Antioxidants, Mitochondrial Dysfunction, and Autophagy in Fibromyalgia

Abstract

Fibromyalgia (FM) is a syndrome that presents primarily in women and is characterized by generalized pain, muscle rigidity, poor quality of sleep, fatigue, cognitive dysfunction, anxiety, episodes of depression, overall sensitivity, and deterioration in the performance of day-to-day activities. In the pathophysiology of fibromyalgia neuroendocrine factors, anomalies of the autonomous nervous system, genetic characteristics, and environmental and psychosocial factors are implicated. Alterations to the cells of the central nervous system that are present in fibromyalgia are due to the toxic effects of free radicals by the high concentrations of polyunsaturated fatty acids of the membranes that are easily oxidized and the low level of protective antioxidant enzymes. In FM, defects are produced in any part of the cycle in the generation of adenosine-5′-triphosphate (ATP) by the mitochondria, which can alter energy production by the mitochondria and cause the characteristic symptoms of FM. The degradation of the mitochondria dependent on autophagy or mitophagy is an important process for maintaining the critical integrity of the mitochondria and limiting the production of reactive oxygen species (ROS). Therefore, the deregulation of autophagy and mitochondrial dysfunction could represent key aspects in the pathophysiology of FM. Management with antioxidants, vitamins, coenzyme Q10, and melatonin, in addition to the antidepressants and structural analogs of the gamma-aminobutyric acid, could modify the florid symptomatology that patients with FM have.

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

“…There is also a related autophagic process called mitophagy to cull dysfunctional mitochondria, such as occurs in fibromyalgia. 54,55 With some cancers, it is generally accepted that autophagy can suppress tumor initiation and cancer growth; and since autophagy blocks growth and increases breakdown of proteins, this is quite logical. 56,57 (Cuervo, 2004(Cuervo, , 2008.…”

“…There is also a related autophagic process called mitophagy to cull dysfunctional mitochondria, such as occurs in fibromyalgia. 54 , 55 …”

“…If the mitochondria are not working effectively, then the process of mitophagy targets them for lysosomal degradation. 54 , 55 The key regulators of this process include the tumor suppressor gene PTEN. 11 5′-Adenosine monophosphate-activated protein kinase (AMPK), for example, will also stimulate mitophagy, as well as new mitochondrial growth, essentially replacing old mitochondria with new ones in a subcellular renewal process ( Figure 2 ).…”

Introductory Chapter: A Challenge to the Concept that Inflammation Plays a Prominent Pathogenic Role in Fibromyalgia

“…Among the chapters in this monograph are those that examine the treatment of fibromyalgia syndrome (FMS) using nonpharmacologic natural products and other relatively novel agents [1][2][3]. Although the modes of therapy described are diverse, a role for disordered immune mechanisms is implicit in each of the three chapters.…”

“…Although the modes of therapy described are diverse, a role for disordered immune mechanisms is implicit in each of the three chapters. These include reference to sulfur springs considered to inhibit interleukin-2 and interferon-gamma [1], introductory explanations of FMS pathogenesis that invokes inflammatory dysfunction [2], and mention of inflammatory cytokine production associated with autonomic nervous system dysfunction-stimulated microglial and astrocyte cell activation [3]. The discussion in the fourth chapter about the impact of FMS on the evaluation of inflammatory diseases assumes the opposite that clinically significant inflammation is not a feature of FMS [4].…”