BMC Musculoskeletal Disorders | |
A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia | |
Manuel Martinez-Lavin1  Maite Vallejo3  Aline Martinez1  Angelica Vargas1  Jose-Manuel Fragoso2  Edith Alvarez-Leon2  Gilberto Vargas-Alarcon2  | |
[1] Department of Rheumatology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico;Department of Molecular Biology, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico;Department of Sociomedical Investigation, National Institute of Cardiology Ignacio Chavez, Mexico city, Mexico | |
关键词: Sodium channelopathy; Neuropathic pain; Autonomic nervous system; Sympathetic nervous system; Dorsal root ganglia; Sympathetic pain; Sodium channels; SCN9A; Fibromyalgia; | |
Others : 1150557 DOI : 10.1186/1471-2474-13-23 |
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received in 2011-05-09, accepted in 2012-02-20, 发布年份 2012 | |
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【 摘 要 】
Background
A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms.
Methods
We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637.
Results
The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001).
Conclusion
In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.
【 授权许可】
2012 Vargas-Alarcon et al; licensee BioMed Central Ltd.
【 预 览 】
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20150405195437578.pdf | 218KB | ![]() |
【 参考文献 】
- [1]Martinez-Lavin M, Solano C: Dorsal root ganglia, sodium channels, and fibromyalgia sympathetic pain. Med Hypotheses 2009, 72:64-66.
- [2]Wada A, Wanke E, Gullo F, Schiavon E: Voltage-dependent Na(v)1.7 sodium channels: multiple roles in adrenal chromaffin cells and peripheral nervous system. Acta Physiol (Oxf) 2008, 192:221-231.
- [3]Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG: A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc Natl Acad Sci USA 2006, 103:8245-850.
- [4]Harty TP, Dib-Hajj SD, Tyrrell L, Blackman R, Hisama FM, Rose JB, Waxman SG: Nav1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive DRG neurons. J Neurosci 2006, 26:12566-12575.
- [5]Dib-Hajj SD, Cummins TR, Black JA, Waxman SG: Sodium channels in normal and pathological pain. Ann Rev Neurosci 2010, 33:325-347.
- [6]Reimann F, Cox JJ, Belfer I, Diatchenko L, Zaykin DV, McHale DP, Drenth JP, Dai F, Wheeler J, Sanders F, Wood L, Wu TX, Karppinen J, Nikolajsen L, Männikkö M, Max MB, Kiselycznyk C, Poddar M, Te Morsche RH, Smith S, Gibson D, Kelempisioti A, Maixner W, Gribble FM, Woods CG: Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci USA 2010, 107:5148-5153.
- [7]Estacion M, Harty TP, Choi JS, Tyrrell L, Dib-Hajj SD, Waxman SG: A sodium channel gene SCN9A polymorphism that increases nociceptor excitability. Ann Neurol 2009, 66:862-866.
- [8]Rivera J, Gonzalez T: The Fibromyalgia Impact Questionnaire: a validated Spanish version to assess health status in women with fibromyalgia. Clin Exp Rheumatol 2004, 22:554-560.
- [9]Vargas-Alarcon G, Fragoso JM, Cruz-Robles D, Vargas A, Vargas A, Lao-Villadoniga JI, Garcia-Fructuoso F, Ramos-Kuri M, Hernandez F, Springall R, Bojalil R, Vallejo M, Martinez-Lavin M: Catechol-O-methyl transferase (COMT) gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis Res Ther 2007, 9(5):R110. BioMed Central Full Text
- [10]Vargas-Alarcón G, Fragoso JM, Cruz-Robles D, Vargas A, Martinez A, Lao-Villadoniga JI, Garcia-Fructuoso F, Vallejo M, Martinez-Lavin M: Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains. Arthritis Rheum 2009, 60:2169-2173.
- [11]Miller A: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988, 16:1215-1217.
- [12]Martinez-Lavin M: Fibromyalgia as a sympathetically maintained pain syndrome. Curr Pain Headache Rep 2004, 5:385-389.
- [13]Martinez-Lavin M: Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res Ther 2007, 9:R216. BioMed Central Full Text
- [14]Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM, Dib-Hajj S, Drenth JP, Waxman SG, Merkies IS: Gain of function Na(V) 1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol 2011, in press.
- [15]Martinez-Lavin M: Fibromyalgia: when distress becomes (un)sympathetic pain. Pain Res Treat 2012, 2012:981565.
- [16]Shen J, Wang HY, Chen JY, Liang BL: Morphologic analysis of normal human lumbar dorsal root ganglion by 3D MR imaging. AJNR Am J Neuroradiol 2006, 27:2098-103.
- [17]Green PG, Alvarez P, Gear RW, Mendoza D, Levine JD: Further validation of a model of fibromyalgia syndrome in the rat. J Pain 2011, 12:811-818.
- [18]Raphael JH, Southall JL, Treharne GJ, Kitas GD: Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome. BMC Musculoskelet Disord 2002, 3:21. BioMed Central Full Text
- [19]Wang SY, Calderon J, Kuo Wang G: Block of neuronal Na+ channels by antidepressant duloxetine in a state-dependent manner. Anesthesiology 2010, 113:655-665.