Study Title:

The Role of Oxidative Stress and Mitochondrial Dysfunction in the Pathogenesis of Fibromyalgia

Study Abstract

Fibromyalgia (FM) is a common pain syndrome accompanied by other symptoms such as
tender spots, decreased pain threshold, fatigue, headache, sleep disturbances, and
depression. It is a chronic condition characterized by a pattern of vague symptoms that are
difficult to diagnose and treat. FM is diagnosed according to the classification criteria
established by the American College of Rheumatology (ACR) (Wolfe et al., 1990) and
routine laboratory investigations usually yield normal results (Yunus et al., 1981). The
prevalence of FM in industrialized countries ranges from 0,4% to 4% (it affects at least 5
million individuals in the United States and 800.000 in Spain) in the population being 11
time more frequent in women than in men (Lawrence et el., 2008). Its high prevalence makes
fibromyalgia a major problem in developed countries in the recent years. FM causes work
absenteeism and has been associated with high medical services utilization cost and
considerable disability. Furthermore, the use of medications and medical necessities
increased markedly across many measures once diagnosis was made. It has been estimated
that annual health service cost of FM patients was twice that of patients with chronic
widespread pain and pain-free controls. The fact that its diagnostic criteria are only clinical,
and that its etiopathogenesis has not yet been clarified makes very difficult the study and
therapeutical approach of the disease. Although the etiology of FM remains unclear,
evidence suggests that biologic, genetic, and environmental factors are involved.It is
considered that the changes in the neuronal activity in the central nervous system, abnormal
metabolism of biogenic amines, immunological disorders and oxidative stress may among
others factors contribute to the development of the disease. For all these reasons is urgent to
do more research in the diagnosis, pathophysiology and therapy of FM.
Fibromyalgia syndrome has been related to disturbances of hypothalamic–pituitary
axis together with neurotransmission imbalance, involving excitatory amino acids,
78 New Insights into Fibromyalgia
catecholamines, substance P and serotonin (5-HT) (Russell et al, 1994; Crofford et al, 1996;
Neeck, 2002). Patient's symptoms may derive from poor stressor modulation, sensitization
of specific nociceptor neurons and pain threshold diminution in response to multiple
environmental factors, such as mechanical or emotional trauma, chronic stress or even
infections. In recent years, new information to our understanding of FM pathophysiology
has emerged. Some genetic polymorphisms and antibodies have been associated with FM,
as the serotoninergic system genotype of 5–HTT (Bazzichi et al., 2006a; Tander et al., 2008),
catechol-O-methytransferase gene polymorphism (Gursoy et al., 2004), D4 dopamine
receptor exon II repeat polymorphism (Buskila et al., 2004), and antibodies against serotonin
(Klein et al., 1992; Werle et al., 2001). It has also been postulated alterations in the
metabolism, transport and reuptake of serotonin (Alnigenis & Barland, 2001; Schwarz et al.,
2002) and substance P (Staud & Spaeth, 2008). Moreover, cytokines homeostasis has been
considered to play a role in the pathogenesis of FM (Wallace, 2001; Wallace et al., 2006).
Conversely, several studies have shown mitochondrial dysfunction and high levels of
oxidative stress markers in FM patients, suggesting that this process may contribute to the
pathophysiology of this disease. However, whether oxidative stress is the cause or the effect
in FM is controversial ( Ozgocmen et al, 2006).

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