Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement
Maria Dehli Vigeland, Siri T. Flåm, Magnus Dehli Vigeland, Ansgar Espeland, Per Martin Kristoffersen, Nils Vetti, Monica Wigemyr, Lars Christian Haugli Bråten, Elisabeth Gjefsen, Elina Iordanova Schistad, Anne Julsrud Haugen, Anne Froholdt, Jan Sture Skouen, John‐Anker Zwart, Kjersti Storheim, Linda M. Pedersen, Benedicte A. Lie, the AIM Study Group, Audny Anke, Bendik S. Winsvold, Britt Elin Lurud, Christian Hellum, Erling Andersen, Fredrik Granvigen, Gunn Hege Marchand, Guro Kjos, Hege Andersen, Hilde Presberg, Ida Beate Øyen Østhus, Jens Ivar Brox, Jörg Aßmus, Karianne Wiger Gammelsrud, Knut Morten Huneide, Lars Grøvle, Mads Peder Rolfsen, Maja Wilhelmsen, Margreth Grotle, Marianne Thorsø, Olav Lutro, Øystein P. Nygaard, Sigrun Randen, Siv Krüger Claussen, Terese Fors, Thomas Kadar, Thor Einar Holmgard, Veronica Sørensen, Vidar Rao
Abstract
Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.