Genetics of chronic pain states

Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel 84101.
Bailli&egrave re s Best Practice and Research in Clinical Rheumatology (Impact Factor: 2.6). 07/2007; 21(3):535-47. DOI: 10.1016/j.berh.2007.02.011
Source: PubMed


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.

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    • "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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    • "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 [34], the majority of investigations on genes involving serotonin function have not shown any association with FMS. For example, Frank et al. [35] found no evidence of any difference in frequency of polymorphisms involving the serotonin receptors 3A or 3B while Tander et al. [36] similarly saw no FMS difference in serotonin receptor 2A polymorphisms, and Gürsoy [37] 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.
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    • "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 [101]. 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 [99] and FM [102]. 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 [103]. "
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