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The phenotypic and genetic signatures of common musculoskeletal pain conditions

Nature Reviews Rheumatology volume 9, pages 340–350 (2013)Cite this article

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Abstract

Musculoskeletal pain conditions, such as fibromyalgia and low back pain, tend to coexist in affected individuals and are characterized by a report of pain greater than expected based on the results of a standard physical evaluation. The pathophysiology of these conditions is largely unknown, we lack biological markers for accurate diagnosis, and conventional therapeutics have limited effectiveness. Growing evidence suggests that chronic pain conditions are associated with both physical and psychological triggers, which initiate pain amplification and psychological distress; thus, susceptibility is dictated by complex interactions between genetic and environmental factors. Herein, we review phenotypic and genetic markers of common musculoskeletal pain conditions, selected based on their association with musculoskeletal pain in previous research. The phenotypic markers of greatest interest include measures of pain amplification and 'psychological' measures (such as emotional distress, somatic awareness, psychosocial stress and catastrophizing). Genetic polymorphisms reproducibly linked with musculoskeletal pain are found in genes contributing to serotonergic and adrenergic pathways. Elucidation of the biological mechanisms by which these markers contribute to the perception of pain in these patients will enable the development of novel effective drugs and methodologies that permit better diagnoses and approaches to personalized medicine.

Key Points

  • Musculoskeletal pain conditions such as low back pain, chronic widespread pain, fibromyalgia and temporomandibular joint disorders are highly prevalent

  • These conditions have measurable phenotypic signatures, which are heterogeneous in nature

  • Musculoskeletal pain conditions have a genetic basis, with both common and rare genetic variants contributing to the conditions and associated endophenotypes

  • Physical and psychological environmental exposures can produce epigenetic effects that alter gene expression, biological pathway activity, and thus the manifestation of clinical phenotypes of musculoskeletal pain conditions

  • Genetic association studies combined with in vitro and in vivo follow-up studies can identify effective therapeutic agents for the treatment of large subpopulations of patients with musculoskeletal pain conditions

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Figure 1: The translational clock—a schematic representation of a novel and rapid approach to identification of new therapeutic targets in commonly observed persistent pain conditions.
Figure 2: The pathological chronic pain circle.

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Acknowledgements

The authors' work is supported in part by grants from NIDCR, NIA and NINDS, R01-DE16558, U01-DE017018, 1K12DSE022793, AG033906, and P01 NS045685. The authors are grateful to Kirsten Ambrose for assistance with preparation of this manuscript.

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Authors and Affiliations

  1. Regional Center for Neurosensory Disorders, Koury Oral Health Sciences Building, University of North Carolina, Chapel Hill, 27599-7455, NC, USA

    Luda Diatchenko, Shad B. Smith & William Maixner

  2. Public Health Services and Research, College of Dentistry, University of Florida, P.O. Box 100404, Gainesville, 32610-0404, FL, USA

    Roger B. Fillingim

Authors
  1. Luda Diatchenko
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  2. Roger B. Fillingim
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All authors contributed equally to each stage of the preparation of this manuscript for publication.

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Correspondence to Luda Diatchenko.

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Competing interests

L. Diatchenko, R. B. Fillingim, S. B. Smith and W. Maixner are consultants for and shareholders in Algynomics.

Supplementary information

Supplementary Table 1

Methods of clinical phenotyping and QST endophenotyping in musculoskeletal pain conditions (DOCX 26 kb)

Supplementary Table 2

Genes implicated in human musculoskeletal pain conditions (DOC 88 kb)

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Diatchenko, L., Fillingim, R., Smith, S. et al. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol 9, 340–350 (2013). https://doi.org/10.1038/nrrheum.2013.43

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