Genetics of chronic pain states
Chronic pain states are common in the general population. Genetic factors can explain a significant amount of the variability in the perception of pain. Fibromyalgia syndrome (FMS) and related conditions are syndromes characterized by generalized pain sensitivity as well as a constellation of other symptoms. Family studies show a strong familial aggregation of FMS and related conditions, suggesting the importance of genetic factors in the development of these conditions. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the pathogenesis of FMS and related conditions. Environmental factors may trigger the development of these disorders in genetically predisposed individuals. Future large well-designed studies are needed to further clarify the role of genetic factors in FMS and related conditions. The knowledge of these gene polymorphisms may help with better subgrouping of FMS patients and in designing a more specific pharmacologic treatment approach.
Available from: Merja Sallinen
- "The precise pathophysiology and etiology of fibromyalgia are yet unknown, but according to the current paradigm, dysfunctions of the autonomic central and peripheral nervous systems, genetics and alterations of the stress regulatory system may explain increased sensitivity to pain and stress in this patient group (Bliddahl & Danneskiold- Samsøe, 2008; Buskila, 2007; Yunus, 2007). Although major stress or adverse life events do not cause fibromyalgia as such, they may account for increased susceptibility to alterations "
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ABSTRACT: In this article we explored narrated life stories of 20 women with a long history of fibromyalgia to reach a deeper understanding of how people interpret the causes and consequences of different life events and illness experiences. Based on narrative analysis, we identified three model narratives that illustrate the different life courses of women with fibromyalgia. In addition, we described a counternarrative that questions fibromyalgia as a chronic disease. In this narrative study, we give insights to the invisible symptoms and unheard experiences that are associated with fibromyalgia and to the ongoing discussion on the etiology and maintenance of fibromyalgia.
Available from: Andrea T White
- "The rationale for this focus was partly that effective and approved pharmacological treatments for FMS included drugs commonly classified as serotonin and norepinephrine reuptake inhibitors (SNRIs). Although a few of the studies have been positive , the majority of investigations on genes involving serotonin function have not shown any association with FMS. For example, Frank et al.  found no evidence of any difference in frequency of polymorphisms involving the serotonin receptors 3A or 3B while Tander et al.  similarly saw no FMS difference in serotonin receptor 2A polymorphisms, and Gürsoy  found no links to serotonin transporter gene variants. "
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ABSTRACT: In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.
Available from: PubMed Central
- "Of utmost interest for clinical application, GST isoforms over-expression has been strongly linked with an early onset of various diseases based on impaired carcinogen detoxification, since GST polymorphisms may reduce glutathione conjugation, one of the major protective mechanisms to modulate reactive metabolite-induced oxidative damage, particularly genotoxic . Polymorphisms of GST single isoenzymes and combinations contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress, and therefore have been correlated with MCS  and FM . The prevalence of neurological symptoms and neuro-muscular pain in MCS, FM, and CFS has also directed investigations towards COMT polymorphisms, since COMT genetic and epigenetic factors are implicated in the impairment of catecholamine regulation, of cognitive tasks, and in the disregulation of nociceptive signalling of NF-kB . "
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ABSTRACT: Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or "medically unexplained symptoms". The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes.
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