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.

Details

Title
Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement
Author
Vigeland Maria Dehli 1 ; Flåm, Siri Tennebø 2 ; Vigeland Magnus Dehli 3 ; Espeland Ansgar 4 ; Kristoffersen, Per Martin 4 ; Vetti Nils 4 ; Wigemyr Monica 5 ; Bråten Lars Christian Haugli 5 ; Gjefsen Elisabeth 1 ; Schistad, Elina Iordanova 6 ; Haugen, Anne Julsrud 7 ; Froholdt, Anne 8 ; Skouen, Jan Sture 9 ; John-Anker, Zwart 1 ; Storheim Kjersti 10 ; Pedersen, Linda Margareth 10 ; Lie, Benedicte Alexandra 2 ; Audny, Anke 11 ; Slagsvold, Winsvold Bendik 5 ; Lurud Britt Elin 12 ; Hellum, Christian 13 ; Andersen, Erling 14 ; Granvigen Fredrik 12 ; Marchand, Gunn Hege 15 ; Kjos Guro 16 ; Andersen, Hege 17 ; Presberg Hilde 18 ; Østhus, Ida Beate 16 ; Brox, Jens Ivar 19 ; Aßmus Jörg 20 ; Gammelsrud Karianne Wiger 21 ; Huneide, Knut Morten 22 ; Grøvle Lars 7 ; Rolfsen, Mads Peder 23 ; Wilhelmsen Maja 11 ; Grotle Margreth 10 ; Thorsø Marianne 22 ; Lutro Olav 24 ; Nygaard, Øystein Petter 25 ; Randen Sigrun 8 ; Claussen Siv Krüger 14 ; Fors Terese 16 ; Kadar, Thomas Istvan 26 ; Holmgard, Thor Einar 27 ; Sørensen, Veronica 22 ; Rao, Vidar 28 

1  Oslo University Hospital, Division of Clinical Neuroscience, Department of Research, Innovation and Education, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); University of Oslo, Faculty of Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
2  Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
3  University of Oslo, Faculty of Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
4  Haukeland University Hospital, Department of Radiology, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393); University of Bergen, Department of Clinical Medicine, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443) 
5  Oslo University Hospital, Division of Clinical Neuroscience, Department of Research, Innovation and Education, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
6  Oslo University Hospital, Department of Physical Medicine and Rehabilitation, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
7  Østfold Hospital Trust, Department of Rheumatology, Grålum, Norway (GRID:grid.412938.5) (ISNI:0000 0004 0627 3923) 
8  Drammen Hospital, Department of Physical Medicine and Rehabilitation, Drammen, Norway (GRID:grid.470118.b) (ISNI:0000 0004 0627 3835) 
9  Haukeland University Hospital, Department of Physical Medicine and Rehabilitation, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393); University of Bergen, Department of Global Public Health and Primary Care, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443) 
10  Oslo University Hospital, Division of Clinical Neuroscience, Department of Research, Innovation and Education, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Oslo Metropolitan University, Department of Physiotherapy, Oslo, Norway (GRID:grid.412414.6) (ISNI:0000 0000 9151 4445) 
11  University Hospital of North Norway, Department of Rehabilitation, Tromsø, Norway (GRID:grid.412244.5) (ISNI:0000 0004 4689 5540); UiT The Arctic University of Norway, Department of Clinical Medicine, Faculty of Health Sciences, Tromsø, Norway (GRID:grid.10919.30) (ISNI:0000000122595234) 
12  Trondheim University Hospital, Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
13  Oslo University Hospital, Department of Orthopaedic Surgery, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
14  Haukeland University Hospital, Department of Clinical Engineering, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393) 
15  Trondheim University Hospital, Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560); Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393) 
16  University Hospital of North Norway, Department of Rehabilitation, Tromsø, Norway (GRID:grid.412244.5) (ISNI:0000 0004 4689 5540) 
17  National Advisory Unit of Spinal Surgery, Trondheim, Norway (GRID:grid.412244.5) 
18  Vestre Viken Hospital, Department of Neurology, Drammen, Norway (GRID:grid.459157.b) (ISNI:0000 0004 0389 7802) 
19  University of Oslo, Faculty of Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Oslo University Hospital, Department of Physical Medicine and Rehabilitation, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
20  Haukeland University Hospital, Centre for Clinical Research, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393) 
21  Oslo University Hospital, Department of Microbiology, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
22  Østfold Hospital Trust, Department of Physical Medicine and Rehabilitation, Grålum, Norway (GRID:grid.412938.5) (ISNI:0000 0004 0627 3923) 
23  University of Oslo, Faculty of Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921); Oslo University Hospital, Department of Orthopaedic Surgery, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
24  Stavanger University Hospital, Stavanger, Norway (GRID:grid.412835.9) (ISNI:0000 0004 0627 2891) 
25  Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, Trondheim, Norway (GRID:grid.5947.f) (ISNI:0000 0001 1516 2393); National Advisory Unit of Spinal Surgery, Trondheim, Norway (GRID:grid.5947.f); Trondheim University Hospital, Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
26  Haukeland University Hospital, Department of Physical Medicine and Rehabilitation, Bergen, Norway (GRID:grid.412008.f) (ISNI:0000 0000 9753 1393) 
27  Norwegian Back Pain Association, Drammen, Norway (GRID:grid.412008.f) 
28  Trondheim University Hospital, Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway (GRID:grid.52522.32) (ISNI:0000 0004 0627 3560) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-021-04189-5
ProQuest document ID
2619581478
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.