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Pain perception is altered by a nucleotide polymorphism in SCN9A.

Publication ,  Journal Article
Reimann, F; Cox, JJ; Belfer, I; Diatchenko, L; Zaykin, DV; McHale, DP; Drenth, JPH; Dai, F; Wheeler, J; Sanders, F; Wood, L; Wu, T-X; Max, MB ...
Published in: Proc Natl Acad Sci U S A
March 16, 2010

The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population. We first genotyped 27 SCN9A SNPs in 578 individuals with a radiographic diagnosis of osteoarthritis and a pain score assessment. A significant association was found between pain score and SNP rs6746030; the rarer A allele was associated with increased pain scores compared to the commoner G allele (P = 0.016). This SNP was then further genotyped in 195 pain-assessed people with sciatica, 100 amputees with phantom pain, 179 individuals after lumbar discectomy, and 205 individuals with pancreatitis. The combined P value for increased A allele pain was 0.0001 in the five cohorts tested (1277 people in total). The two alleles of the SNP rs6746030 alter the coding sequence of the sodium channel Nav1.7. Each was separately transfected into HEK293 cells and electrophysiologically assessed by patch-clamping. The two alleles showed a difference in the voltage-dependent slow inactivation (P = 0.042) where the A allele would be predicted to increase Nav1.7 activity. Finally, we genotyped 186 healthy females characterized by their responses to a diverse set of noxious stimuli. The A allele of rs6746030 was associated with an altered pain threshold and the effect mediated through C-fiber activation. We conclude that individuals experience differing amounts of pain, per nociceptive stimulus, on the basis of their SCN9A rs6746030 genotype.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 16, 2010

Volume

107

Issue

11

Start / End Page

5148 / 5153

Location

United States

Related Subject Headings

  • Sodium Channels
  • Regression Analysis
  • Polymorphism, Single Nucleotide
  • Perception
  • Pain Threshold
  • Pain
  • NAV1.7 Voltage-Gated Sodium Channel
  • Mutant Proteins
  • Humans
  • Genetic Predisposition to Disease
 

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Reimann, F., Cox, J. J., Belfer, I., Diatchenko, L., Zaykin, D. V., McHale, D. P., … Woods, C. G. (2010). Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A, 107(11), 5148–5153. https://doi.org/10.1073/pnas.0913181107
Reimann, Frank, James J. Cox, Inna Belfer, Luda Diatchenko, Dmitri V. Zaykin, Duncan P. McHale, Joost P. H. Drenth, et al. “Pain perception is altered by a nucleotide polymorphism in SCN9A.Proc Natl Acad Sci U S A 107, no. 11 (March 16, 2010): 5148–53. https://doi.org/10.1073/pnas.0913181107.
Reimann F, Cox JJ, Belfer I, Diatchenko L, Zaykin DV, McHale DP, et al. Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5148–53.
Reimann, Frank, et al. “Pain perception is altered by a nucleotide polymorphism in SCN9A.Proc Natl Acad Sci U S A, vol. 107, no. 11, Mar. 2010, pp. 5148–53. Pubmed, doi:10.1073/pnas.0913181107.
Reimann F, Cox JJ, Belfer I, Diatchenko L, Zaykin DV, McHale DP, Drenth JPH, Dai F, Wheeler J, Sanders F, Wood L, Wu T-X, Karppinen J, Nikolajsen L, Männikkö M, Max MB, Kiselycznyk C, Poddar M, Te Morsche RHM, 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 U S A. 2010 Mar 16;107(11):5148–5153.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 16, 2010

Volume

107

Issue

11

Start / End Page

5148 / 5153

Location

United States

Related Subject Headings

  • Sodium Channels
  • Regression Analysis
  • Polymorphism, Single Nucleotide
  • Perception
  • Pain Threshold
  • Pain
  • NAV1.7 Voltage-Gated Sodium Channel
  • Mutant Proteins
  • Humans
  • Genetic Predisposition to Disease