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Cited by 85Pain Mechanisms and TreatmentsPain Management and TreatmentMusculoskeletal pain and rehabilitation

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Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain

Parisien, Marc, Samoshkin, Alexander, Tansley, Shannon N., Piltonen, Marjo H., Martin, Loren J., El-Hachem, Nehme, Dagostino, Concetta, Allegri, Massimo, Mogil, Jeffrey S., Khoutorsky, Arkady, Diatchenko, Luda·2019·Pain
DOI 10.1097/j.pain.0000000000001471
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Abstract

Chronic pain is a debilitating and poorly treated condition whose underlying mechanisms are poorly understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with pain processing, supporting molecular and cellular mechanisms that maintain painful states. However, it is not known whether transcriptome changes can be used to reconstruct a molecular pathophysiology of pain. In the current study, we identify molecular pathways contributing to chronic pain states through the analysis of global changes in the transcriptome of dorsal root ganglia, spinal cord, brain, and blood in mouse assays of nerve injury– and inflammation-induced pain. Comparative analyses of differentially expressed genes identified substantial similarities between 2 animal pain assays and with human low-back pain. Furthermore, the extracellular matrix (ECM) organization has been found the most commonly regulated pathway across all tested tissues in the 2 animal assays. Examination of human genome-wide association study data sets revealed an overrepresentation of differentially expressed genes within the ECM organization pathway in single nucleotide polymorphisms most strongly associated with human back pain. In summary, our comprehensive transcriptomics analysis in mouse and human identified ECM organization as a central molecular pathway in the development of chronic pain.

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Metadata

Authors
Parisien, M., Samoshkin, A., Tansley, S. N., Piltonen, M. H., Martin, L. J., El-Hachem, N., Dagostino, C., Allegri, M., Mogil, J. S., Khoutorsky, A., & Diatchenko, L.
Affiliations
  • McGill University (CA)
  • University of Cambridge (GB)
  • University of Toronto (CA)
  • Alan Edwards Centre for Research on Pain, McGill University, Montréal, QC, Canada
  • University of Parma (IT)
  • Azienda Ospedaliera San Gerardo (IT)
Corresponding author
Diatchenko, Luda
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-01-03
Volume
160
Issue
4
Pages
932-944
ISSN
  • 0304-3959 (ISSN-L)
  • 1872-6623
DOI
10.1097/j.pain.0000000000001471
OpenAlex
W2910729187
Semantic Scholar
0b031cb00b897a758012a18ac5cf8deccf162e19
Cited by
85
References
78
Citations by year
2026: 12 · 2025: 11 · 2024: 14 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 11 · 2019: 3
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
  • Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
Keywords
chronic pain, neuropathic pain, inflammatory pain, extracellular matrix organization, dorsal root ganglia, spinal cord transcriptome, brain transcriptome, blood transcriptome, nerve injury, low back pain, single nucleotide polymorphisms, gene expression changes
MeSH terms
Animals, Disease Models, Animal, Extracellular Matrix, Female, Freund's Adjuvant, Genetic Testing, Humans, Inflammation, Mice, Inbred BALB C, Neuralgia, Pain Measurement, RNA, Messenger, Polymorphism, Single Nucleotide, Mice, Gene Regulatory Networks, Genetic Association Studies, Transcriptome

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