Facial pain with localized and widespread manifestations: Separate pathways of vulnerability

Gary D. Slade, Shad B. Smith, Dmitri V. Zaykin, Inna E. Tchivileva, Dustin G. Gibson, Anton Yuryev, Ilya Mazo, Eric Bair, Roger Fillingim, Richard Ohrbach, Joel Greenspan, William Maixner, Luda Diatchenko

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2335-2343
Number of pages9
JournalPain
Volume154
Issue number11
DOIs
StatePublished - Nov 2013
Externally publishedYes

Keywords

  • Case-control study
  • Human genetics
  • Serotonergic receptor
  • Temporomandibular disorder

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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  • Cite this

    Slade, G. D., Smith, S. B., Zaykin, D. V., Tchivileva, I. E., Gibson, D. G., Yuryev, A., Mazo, I., Bair, E., Fillingim, R., Ohrbach, R., Greenspan, J., Maixner, W., & 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