A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

Vargas‐Alarcón, Gilberto; Álvarez-León, Edith; Fragoso, J.M.; Vargas, Angélica; Martínez, Agustín Méndez; Vallejo, Maité; Martı́nez-Lavı́n, Manuel

doi:10.1186/1471-2474-13-23

Cited by 79 publications

(43 citation statements)

References 17 publications

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“…A sodium channel isoform (NaV1.7) encoded in gene SCN9A of chromosome 2q24.3 is predominantly expressed in the dorsal root ganglia pain-sensing neurons and sympathetic ganglia neurons and their fine-diameter axons. In a pilot study, we described a particular SCN9A sodium channel gene variant (rs6754031 GG genotype) associated with severe fibromyalgia (27). On the other hand, Faber et al reported that a gain of function mutations in sodium channel NaV1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28 %) of patients meeting strict criteria for small fiber neuropathy (28).…”

Section: Discussionmentioning

confidence: 92%

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy

Ramı́rez

Martínez-Martínez

Hernández-Quíntela

et al. 2015

Seminars in Arthritis and Rheumatism

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Section: Discussionmentioning

confidence: 92%

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy

Ramı́rez

Martínez-Martínez

Hernández-Quíntela

et al. 2015

Seminars in Arthritis and Rheumatism

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“…SFPN has more recently been linked to gain-of-function mutations in the SCN9A gene encoding the Nav1.7 sodium-channel isoform that is preferentially expressed in small-fiber nociceptive neurons, but commercial tests are not yet available [10]. FMS has also been recently associated with a specific SCN9A polymorphism [46], providing potential additional evidence of convergence between FMS and SFPN. Although there is no cure for the genetic forms of SFPN yet, a trial of L-serine is underway for HSAN-1 [14], and identifying specific mutations can guide patients towards targeted therapies not usually considered for FMS patients, such as sodium-channel blockers.…”

Section: Discussionmentioning

confidence: 99%

Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia

Oaklander

Herzog

Downs

et al. 2013

Pain

266

186

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Fibromyalgia is a common, disabling, syndrome that includes chronic widespread pain plus other diverse symptoms. No specific objective abnormalities have been identified, precluding definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by dysfunction and degeneration of peripheral small-fiber neurons. SFPN has established etiologies, some diagnosable and definitively treatable, e.g., diabetes. To evaluate the hypothesis that some patients labeled with “fibromyalgia” have unrecognized SFPN causing their illness symptoms, we analyzed SFPN-associated symptoms, signs, and pathological and physiological markers in 27 fibromyalgia patients and 30 matched normal controls. Fibromyalgia subjects had to satisfy American College of Rheumatology criteria plus present documented evidence of a physician’s actual fibromyalgia diagnosis. Study instruments comprised the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, plus autonomic-function testing (AFT). 41% of skin biopsies from fibromyalgia subjects vs. 3% of biopsies from control subjects were diagnostic for SFPN, and MNSI and UENS scores were higher among fibromyalgia than control subjects (all P ≤ 0.001). Abnormal AFTs were equally prevalent suggesting that fibromyalgia-associated SFPN is primarily somatic. Blood tests from all 13 fibromyalgia subjects with SFPN-diagnostic skin biopsies provided insights into etiologies. All glucose tolerance tests were normal, but eight subjects had dysimmune markers, 2 had hepatitis C serologies, and one family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as “fibromyalgia” have unrecognized small-fiber polyneuropathy, a distinct disease that can be objectively tested for and sometimes definitively treated.

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“…In rats, its expression has been documented both in the central projections and in the peripheral terminals of these DRG neurons with strong immunoreactivity in intra-epidermal nerve fibers [469]. Investigation of ten SNPs in the SCN9A gene showed that one of them was associated with severe FMS in Mexican patients [470]. Altogether, these data raise the possibility that a DRG sodium channelopathy could underlie some cases of FMS, particularly those associated with, or presenting as, a small fiber neuropathy.…”

Section: Potential Pathogenetic Mechanisms Genetics and Epigeneticsmentioning

confidence: 92%

Fibromyalgia: A Critical and Comprehensive Review

Borchers

Gershwin

2015

Clinic Rev Allerg Immunol

229

217

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Fibromyalgia is a disorder that is part of a spectrum of syndromes that lack precise classification. It is often considered as part of the global overview of functional somatic syndromes that are otherwise medically unexplained or part of a somatization disorder. Patients with fibromyalgia share symptoms with other functional somatic problems, including issues of myalgias, arthralgias, fatigue and sleep disturbances. Indeed, there is often diagnostic and classification overlap for the case definitions of a variety of somatization disorders. Fibromyalgia, however, is a critically important syndrome for physicians and scientists to be aware of. Patients should be taken very seriously and provided optimal care. Although inflammatory, infectious, and autoimmune disorders have all been ascribed to be etiological events in the development of fibromyalgia, there is very little data to support such a thesis. Many of these disorders are associated with depression and anxiety and may even be part of what has been sometimes called affected spectrum disorders. There is no evidence that physical trauma, i.e., automobile accidents, is associated with the development or exacerbation of fibromyalgia. Treatment should be placed on education, patient support, physical therapy, nutrition, and exercise, including the use of drugs that are approved for the treatment of fibromyalgia. Treatment should not include opiates and patients should not become poly pharmacies in which the treatment itself can lead to significant morbidities. Patients with fibromyalgia are living and not dying of this disorder and positive outlooks and family support are key elements in the management of patients.

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A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

Cited by 79 publications

References 17 publications

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy

Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia

Fibromyalgia: A Critical and Comprehensive Review

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