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Facial pain with localized and widespread manifestations: separate pathways of vulnerability.

Publication ,  Journal Article
Slade, GD; Smith, SB; Zaykin, DV; Tchivileva, IE; Gibson, DG; Yuryev, A; Mazo, I; Bair, E; Fillingim, R; Ohrbach, R; Greenspan, J; Maixner, W ...
Published in: Pain
November 2013

Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P=0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P=0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P=1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P=0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P=1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.

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Published In

Pain

DOI

EISSN

1872-6623

Publication Date

November 2013

Volume

154

Issue

11

Start / End Page

2335 / 2343

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Signal Transduction
  • Sex Characteristics
  • Serotonin
  • Risk
  • Receptors, Antigen, T-Cell
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Odds Ratio
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Slade, G. D., Smith, S. B., Zaykin, D. V., Tchivileva, I. E., Gibson, D. G., Yuryev, A., … Diatchenko, L. (2013). Facial pain with localized and widespread manifestations: separate pathways of vulnerability. Pain, 154(11), 2335–2343. https://doi.org/10.1016/j.pain.2013.07.009
Slade, Gary D., Shad B. Smith, Dmitri V. Zaykin, Inna E. Tchivileva, Dustin G. Gibson, Anton Yuryev, Ilya Mazo, et al. “Facial pain with localized and widespread manifestations: separate pathways of vulnerability.Pain 154, no. 11 (November 2013): 2335–43. https://doi.org/10.1016/j.pain.2013.07.009.
Slade GD, Smith SB, Zaykin DV, Tchivileva IE, Gibson DG, Yuryev A, et al. Facial pain with localized and widespread manifestations: separate pathways of vulnerability. Pain. 2013 Nov;154(11):2335–43.
Slade, Gary D., et al. “Facial pain with localized and widespread manifestations: separate pathways of vulnerability.Pain, vol. 154, no. 11, Nov. 2013, pp. 2335–43. Pubmed, doi:10.1016/j.pain.2013.07.009.
Slade GD, Smith SB, Zaykin DV, Tchivileva IE, Gibson DG, Yuryev A, Mazo I, Bair E, Fillingim R, Ohrbach R, Greenspan J, Maixner W, Diatchenko L. Facial pain with localized and widespread manifestations: separate pathways of vulnerability. Pain. 2013 Nov;154(11):2335–2343.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

November 2013

Volume

154

Issue

11

Start / End Page

2335 / 2343

Location

United States

Related Subject Headings

  • Young Adult
  • Temporomandibular Joint Disorders
  • Signal Transduction
  • Sex Characteristics
  • Serotonin
  • Risk
  • Receptors, Antigen, T-Cell
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Odds Ratio