{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:09:59Z","timestamp":1767625799260,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Helse S\u00f8r-\u00d8st","award":["2015090","911938","911891","2017201"],"award-info":[{"award-number":["2015090","911938","911891","2017201"]}]},{"name":"Helse Vest","award":["2015090","911938","911891","2017201"],"award-info":[{"award-number":["2015090","911938","911891","2017201"]}]},{"name":"Klinbeforsk","award":["2015090","911938","911891","2017201"],"award-info":[{"award-number":["2015090","911938","911891","2017201"]}]},{"name":"REMEDY young researcher program","award":["2015090","911938","911891","2017201"],"award-info":[{"award-number":["2015090","911938","911891","2017201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic low back pain (cLBP) lacks clear physiological explanations, and the treatment options are of limited effect. We aimed to elucidate the underlying biology of cLBP in a subgroup of patients with Modic changes type I (suggestive of inflammatory vertebral bone marrow lesions) by correlating gene expression in blood with patient-reported outcomes on disability and pain intensity and explore sex differences. Patients were included from the placebo group of a clinical study on patients with cLBP and Modic changes. Blood was collected at the time of inclusion, after three months, and after one year, and gene expression was measured at all time points by high-throughput RNA sequencing. The patients reported disability using the Roland\u2013Morris Disability Questionnaire, and pain intensity was assessed as a mean of three scores on a 0\u201310 numeric rating scale: current LBP, worst LBP within the last two weeks, and mean LBP within the last two weeks. The gene expression profiles were then correlated to the reported outcomes. Changes in gene expression over time correlated significantly with changes in both disability and pain. The findings showed distinct patterns in men and women, with negligible overlap in correlated genes between the sexes. The genes involved were enriched in immunological pathways, particularly T cell receptor complex and immune responses related to neutrophils. Several of the genes harbour polymorphisms that previously have been found to be associated with chronic pain. Taken together, our results indicate gender differences in the underlying biology of disability and pain intensity in patients with low back pain.<\/jats:p>","DOI":"10.3390\/ijms26020800","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gene Expression Correlates with Disability and Pain Intensity in Patients with Chronic Low Back Pain and Modic Changes in a Sex-Specific Manner"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-5491","authenticated-orcid":false,"given":"Maria Dehli","family":"Vigeland","sequence":"first","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Faculty of Medicine, University of Oslo, 0316 Oslo, Norway"},{"name":"Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siri Tenneb\u00f8","family":"Fl\u00e5m","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9134-4962","authenticated-orcid":false,"given":"Magnus Dehli","family":"Vigeland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Oslo, 0316 Oslo, Norway"},{"name":"Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Zucknick","sequence":"additional","affiliation":[{"name":"Oslo Centre for Biostatistics and Epidemiology, University of Oslo, 0316 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Wigemyr","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-2556","authenticated-orcid":false,"given":"Lars Christian Haugli","family":"Br\u00e5ten","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0470-7225","authenticated-orcid":false,"given":"Elisabeth","family":"Gjefsen","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Faculty of Medicine, University of Oslo, 0316 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5721-0154","authenticated-orcid":false,"given":"John-Anker","family":"Zwart","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Faculty of Medicine, University of Oslo, 0316 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjersti","family":"Storheim","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Department of Rehabilitation Science and Health Technology, Oslo Metropolitan University, 0130 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8448-983X","authenticated-orcid":false,"given":"Linda Margareth","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, 0450 Oslo, Norway"},{"name":"Department of Rehabilitation Science and Health Technology, Oslo Metropolitan University, 0130 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-7004","authenticated-orcid":false,"given":"Benedicte Alexandra","family":"Lie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Oslo, 0316 Oslo, Norway"},{"name":"Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the AIM Study 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Orthop. Transl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/ner.12018","article-title":"Epidemiology of low back pain in adults","volume":"17","author":"Manchikanti","year":"2014","journal-title":"Neuromodulation J. Int. Neuromodulation Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1016\/S0140-6736(18)30489-6","article-title":"Prevention and treatment of low back pain: Evidence, challenges, and promising directions","volume":"391","author":"Foster","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0140-6736(16)30970-9","article-title":"Non-specific low back pain","volume":"389","author":"Maher","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","article-title":"What low back pain is and why we need to pay attention","volume":"391","author":"Hartvigsen","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1148\/radiology.166.1.3336678","article-title":"Degenerative disk disease: Assessment of changes in vertebral body marrow with MR imaging","volume":"166","author":"Modic","year":"1988","journal-title":"Radiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s005860050091","article-title":"Vertebral end-plate (Modic) changes on lumbar spine MRI: Correlation with pain reproduction at lumbar discography","volume":"7","author":"Braithwaite","year":"1998","journal-title":"Eur. Spine J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1097\/01.brs.0000224167.18483.14","article-title":"A three-year follow-up of lumbar spine endplate (Modic) changes","volume":"31","author":"Kuisma","year":"2006","journal-title":"Spine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/art.20236","article-title":"Structural, psychological, and genetic influences on low back and neck pain: A study of adult female twins","volume":"51","author":"MacGregor","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.pain.2007.01.010","article-title":"Heritability of low back pain and the role of disc degeneration","volume":"131","author":"Battie","year":"2007","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1002\/ejp.506","article-title":"Heritability and lifestyle factors in chronic low back pain: Results of the Australian twin low back pain study (The AUTBACK study)","volume":"18","author":"Junqueira","year":"2014","journal-title":"Eur. J. Pain"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Suri, P., Palmer, M.R., Tsepilov, Y.A., Freidin, M.B., Boer, C.G., Yau, M.S., Evans, D.S., Gelemanovic, A., Bartz, T.M., and Nethander, M. (2018). Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007601"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/j.pain.0000000000001514","article-title":"Insight into the genetic architecture of back pain and its risk factors from a study of 509,000 individuals","volume":"160","author":"Freidin","year":"2019","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1097\/j.pain.0000000000002100","article-title":"Sex- and age-specific genetic analysis of chronic back pain","volume":"162","author":"Freidin","year":"2021","journal-title":"Pain"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Johnston, K.J.A., Adams, M.J., Nicholl, B.I., Ward, J., Strawbridge, R.J., Ferguson, A., McIntosh, A.M., Bailey, M.E.S., and Smith, D.J. (2019). Genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008164"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-021-04103-z","article-title":"Exome sequencing and analysis of 454,787 UK Biobank participants","volume":"599","author":"Backman","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1136\/annrheumdis-2020-219624","article-title":"Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain","volume":"80","author":"Rahman","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1744806921999924","DOI":"10.1177\/1744806921999924","article-title":"Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia","volume":"17","author":"Nishizawa","year":"2021","journal-title":"Mol. Pain"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Johnston, K.J.A., Ward, J., Ray, P.R., Adams, M.J., McIntosh, A.M., Smith, B.H., Strawbridge, R.J., Price, T.J., Smith, D.J., and Nicholl, B.I. (2021). Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009428"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/bs.irn.2022.06.013","article-title":"Sex and gender differences in pain","volume":"164","author":"Osborne","year":"2022","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nrn3360","article-title":"Sex differences in pain and pain inhibition: Multiple explanations of a controversial phenomenon","volume":"13","author":"Mogil","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jpain.2011.11.002","article-title":"Sex Differences in Reported Pain Across 11,000 Patients Captured in Electronic Medical Records","volume":"13","author":"Ruau","year":"2012","journal-title":"J. Pain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.pain.2011.05.002","article-title":"Sex differences in perceived pain are affected by an anxious brain","volume":"152","author":"Goffaux","year":"2011","journal-title":"Pain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1080\/09638288.2018.1424950","article-title":"The impact of age and gender on the ICF-based assessment of chronic low back pain","volume":"41","author":"Fehrmann","year":"2019","journal-title":"Disabil. Rehabil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1097\/BRS.0b013e3181ba1531","article-title":"The Impact of Body Mass Index on the Prevalence of Low Back Pain: The HUNT Study","volume":"35","author":"Heuch","year":"2010","journal-title":"Spine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e000972","DOI":"10.1136\/bmjsem-2020-000972","article-title":"Sex and gender considerations in low back pain clinical practice guidelines: A scoping review","volume":"6","author":"Rathbone","year":"2020","journal-title":"BMJ Open Sport Exerc. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1179\/crn.2004.030","article-title":"Reproducibility of visual analog scale (VAS) pain scores to mechanical pressure","volume":"22","author":"Goddard","year":"2004","journal-title":"Cranio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S240","DOI":"10.1002\/acr.20543","article-title":"Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)","volume":"63","author":"Hawker","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/j.pain.0000000000000775","article-title":"Individual differences in pain: Understanding the mosaic that makes pain personal","volume":"158","author":"Fillingim","year":"2017","journal-title":"Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8538","DOI":"10.1073\/pnas.1430684100","article-title":"Neural correlates of interindividual differences in the subjective experience of pain","volume":"100","author":"Coghill","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.pain.2013.12.004","article-title":"Pain sensitivity is inversely related to regional grey matter density in the brain","volume":"155","author":"Emerson","year":"2014","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12938","DOI":"10.1073\/pnas.0503264102","article-title":"Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene","volume":"102","author":"Mogil","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","first-page":"1022","article-title":"Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis","volume":"17","author":"Ferraz","year":"1990","journal-title":"J. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0304-3959(95)00214-6","article-title":"Gender variations in clinical pain experience","volume":"65","author":"Unruh","year":"1996","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0304-3959(97)00199-1","article-title":"Sex differences in the perception of noxious experimental stimuli: A meta-analysis","volume":"74","author":"Riley","year":"1998","journal-title":"Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.pain.2011.11.025","article-title":"A systematic literature review of 10 years of research on sex\/gender and experimental pain perception\u2014Part 1: Are there really differences between women and men?","volume":"153","author":"Racine","year":"2012","journal-title":"Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.jpain.2008.12.001","article-title":"Sex, gender, and pain: A review of recent clinical and experimental findings","volume":"10","author":"Fillingim","year":"2009","journal-title":"J. Pain"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.pain.2007.02.006","article-title":"Cross-sex hormone administration changes pain in transsexual women and men","volume":"132","author":"Aloisi","year":"2007","journal-title":"Pain"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Athnaiel, O., Cantillo, S., Paredes, S., and Knezevic, N.N. (2023). The Role of Sex Hormones in Pain-Related Conditions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031866"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.pain.2013.04.028","article-title":"Pain modality- and sex-specific effects of COMT genetic functional variants","volume":"154","author":"Belfer","year":"2013","journal-title":"Pain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9831","DOI":"10.1523\/JNEUROSCI.1742-12.2012","article-title":"Pain intensity the first year after lumbar disc herniation is associated with the A118G polymorphism in the opioid receptor mu 1 gene: Evidence of a sex and genotype interaction","volume":"32","author":"Olsen","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1155\/2015\/490610","article-title":"Associations between gender, coping patterns and functioning for individuals with chronic pain: A systematic review","volume":"20","author":"Strong","year":"2015","journal-title":"Pain Res. Manag."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/bja\/aet127","article-title":"Sex differences in pain: A brief review of clinical and experimental findings","volume":"111","author":"Bartley","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e1018","DOI":"10.1097\/PR9.0000000000001018","article-title":"Brain-specific genes contribute to chronic but not to acute back pain","volume":"7","author":"Bortsov","year":"2022","journal-title":"Pain Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.2147\/JPR.S134745","article-title":"A systematic review of sex differences in the placebo and the nocebo effect","volume":"10","author":"Vambheim","year":"2017","journal-title":"J. Pain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s41467-022-28167-1","article-title":"Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology","volume":"13","author":"Bjornsdottir","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tsepilov, Y.A., Freidin, M.B., Shadrina, A.S., Sharapov, S.Z., Elgaeva, E.E., Zundert, J.V., Karssen, L., Suri, P., Williams, F.M.K., and Aulchenko, Y.S. (2020). Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-1051-9"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1093\/rheumatology\/keaa847","article-title":"An association between chronic widespread pain and the gut microbiome","volume":"60","author":"Freidin","year":"2021","journal-title":"Rheumatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/s41562-024-01909-5","article-title":"Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation","volume":"8","author":"Carey","year":"2024","journal-title":"Nat. Hum. Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12974-016-0607-6","article-title":"Interleukin-6: An emerging regulator of pathological pain","volume":"13","author":"Zhou","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1007\/s00586-023-07717-1","article-title":"The importance of inflammatory biomarkers in non-specific acute and chronic low back pain: A systematic review","volume":"32","author":"Pinto","year":"2023","journal-title":"Eur. Spine J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2015.01.008","article-title":"Serum levels of the pro-inflammatory interleukins 6 (IL-6) and -8 (IL-8) in patients with lumbar radicular pain due to disc herniation: A 12-month prospective study","volume":"46","author":"Pedersen","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/hmg\/ddi013","article-title":"Genetic basis for individual variations in pain perception and the development of a chronic pain condition","volume":"14","author":"Diatchenko","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Vetterlein, A., Monzel, M., and Reuter, M. (2023). Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all?\u2014A review and meta-analysis. Neurosci. Biobehav. Rev., 148.","DOI":"10.1016\/j.neubiorev.2023.105112"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/16501970306094","article-title":"Cross-cultural adaptation of the Norwegian versions of the Roland-Morris Disability Questionnaire and the Oswestry Disability Index","volume":"35","author":"Grotle","year":"2003","journal-title":"J. Rehabil. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e3495","DOI":"10.1097\/MD.0000000000003495","article-title":"Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability","volume":"95","author":"Maatta","year":"2016","journal-title":"Medicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00586-013-3036-6","article-title":"Inflammatory pain pattern and pain with lumbar extension associated with Modic 1 changes on MRI: A prospective case-control study of 120 patients","volume":"23","author":"Bailly","year":"2014","journal-title":"Eur. Spine J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1097\/j.pain.0000000000002215","article-title":"Sex differences in neuroimmune and glial mechanisms of pain","volume":"162","author":"Gregus","year":"2021","journal-title":"Pain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nn.4053","article-title":"Different immune cells mediate mechanical pain hypersensitivity in male and female mice","volume":"18","author":"Sorge","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eabj9954","DOI":"10.1126\/scitranslmed.abj9954","article-title":"Acute inflammatory response via neutrophil activation protects against the development of chronic pain","volume":"14","author":"Parisien","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Vigeland, M.D., Fl\u00e5m, S.T., Vigeland, M.D., Espeland, A., Zucknick, M., Wigemyr, M., Br\u00e5ten, L.C., Gjefsen, E., Zwart, J.-A., and Storheim, K. (2023). Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes. Antibiotics, 12.","DOI":"10.3390\/antibiotics12071217"},{"key":"ref_62","first-page":"l5654","article-title":"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): Double blind, randomised, placebo controlled, multicentre trial","volume":"367","author":"Rolfsen","year":"2019","journal-title":"BMJ Clin. Res. Ed."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1186\/s13063-017-2306-8","article-title":"Antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): Study protocol for a randomised controlled trial","volume":"18","author":"Storheim","year":"2017","journal-title":"Trials"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kongsted, A., Hestb\u00e6k, L., and Kent, P. (2017). How can latent trajectories of back pain be translated into defined subgroups?. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1644-8"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gatchel, R.J., Bevers, K., Licciardone, J.C., Su, J., Du, Y., and Brotto, M. (2018). Transitioning from Acute to Chronic Pain: An Examination of Different Trajectories of Low-Back Pain. Healthcare, 6.","DOI":"10.3390\/healthcare6020048"},{"key":"ref_66","unstructured":"Bakdash, J.Z., and Marusich, L.R. (2024, November 23). rmcorr: Repeated Measures Correlation. R Package Version 0.7.0. Available online: https:\/\/lmarusich.github.io\/rmcorr\/."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/bioinformatics\/btv566","article-title":"Qualimap 2: Advanced multi-sample quality control for high-throughput sequencing data","volume":"32","author":"Okonechnikov","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_68","unstructured":"Andrews, S. (2024, November 23). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D745","DOI":"10.1093\/nar\/gky1113","article-title":"Ensembl 2019","volume":"47","author":"Cunningham","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Vigeland, M.D., Fl\u00e5m, S.T., Vigeland, M.D., Espeland, A., Kristoffersen, P.M., Vetti, N., Wigemyr, M., Br\u00e5ten, L.C.H., Gjefsen, E., and Schistad, E.I. (2022). Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement. Sci. Rep., 12.","DOI":"10.1038\/s41598-021-04189-5"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gentleman, R., Carey, V.J., Huber, W., Irizarry, R.A., and Dudoit, S. (2005). limma: Linear Models for Microarray Data. Bioinformatics and Computational Biology Solutions Using R and Bioconductor, Springer.","DOI":"10.1007\/0-387-29362-0"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Law, C.W., Chen, Y., Shi, W., and Smyth, G.K. (2014). voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"van Iterson, M., van Zwet, E.W., Heijmans, B.T., and the BIOS Consortium (2017). Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution. Genome Biol., 18.","DOI":"10.1186\/s13059-016-1131-9"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eaax9198","DOI":"10.1126\/science.aax9198","article-title":"A genome-wide transcriptomic analysis of protein-coding genes in human blood cells","volume":"366","author":"Uhlen","year":"2019","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:27Z","timestamp":1759919487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,18]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020800"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020800","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,1,18]]}}}