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

Parisien, Marca; Samoshkin, Alexandera,b; Tansley, Shannon N.a; Piltonen, Marjo H.a; Martin, Loren J.c; El-Hachem, Nehmea; Dagostino, Concettad,e; Allegri, Massimof,g; Mogil, Jeffrey S.a,h; Khoutorsky, Arkadya,i; Diatchenko, Ludaa,*

doi: 10.1097/j.pain.0000000000001471
Research Paper

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.

The extracellular matrix organization pathway was found a major contributor to both inflammatory and chronic pain etiologies, including risk for back pain from human genome-wide association study.

aAlan Edwards Centre for Research on Pain, McGill University, Montre[Combining Acute Accent]al, QC, Canada

bSchool of the Clinical Medicine, University of Cambridge, Cambridge, United Kingdom

cDepartment of Psychology, University of Toronto, Mississauga, ON, Canada

dDepartment of Medicine and Surgery, University of Parma, Parma, Italy

eStudy In Multidisciplinary Pain Research (SIMPAR), Parma, Italy

fItalian Pain Group, Milan, Italy

gPain Therapy Service, Policlinico Monza Hospital, Monza, Italy

Departments of hPsychology and

iAnesthesia, McGill University, Montre[Combining Acute Accent]al, QC, Canada

Corresponding author. Address: Alan Edwards Centre for Research on Pain Genome Building, Room 2201, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada H3A 0G1. Tel.: 514-398-2878; fax: 514-398-8900. E-mail address: (L. Diatchenko).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

M. Parisien and A. Samoshkin contributed equally to this work.

Received October 22, 2018

Received in revised form December 06, 2018

Accepted December 14, 2018

© 2019 International Association for the Study of Pain
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