RESUMO
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.
Assuntos
Medula Óssea/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Perfilação da Expressão Gênica , Dor Lombar/diagnóstico por imagem , Imageamento por Ressonância Magnética , Coluna Vertebral/diagnóstico por imagem , Transcriptoma , Adulto , Medula Óssea/imunologia , Dor Crônica/genética , Dor Crônica/imunologia , Feminino , Regulação da Expressão Gênica , Humanos , Dor Lombar/genética , Dor Lombar/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Coluna Vertebral/imunologiaRESUMO
BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide, but the aetiology remains poorly understood. Finding relevant biomarkers may lead to better understanding of disease mechanisms. Patients with vertebral endplate bone marrow lesions visualised on MRI as Modic changes (MCs) have been proposed as a distinct LBP phenotype, and inflammatory mediators may be involved in the development of MCs. OBJECTIVES: To identify possible serum biomarkers for LBP in patients with MCs. METHODS: In this case control study serum levels of 40 cytokines were compared between patients with LBP and MC type 1 (n=46) or type 2 (n=37) and healthy controls (n=50). RESULTS: Analyses identified significantly higher levels of six out of 40 cytokines in the MC type 1 group (MC1), and five in the MC type 2 group (MC2) compared with healthy controls. Six cytokines were moderately correlated with pain. Principal component analyses revealed clustering and separation of patients with LBP and controls, capturing 40.8% of the total variance, with 10 cytokines contributing to the separation. Macrophage migration inhibitory factor (MIF) alone accounted for 92% of the total contribution. Further, receiver operating characteristics analysis revealed that MIF showed an acceptable ability to distinguish between patients and controls (area under the curve=0.79). CONCLUSIONS: These results suggest that cytokines may play a role in LBP with MCs. The clinical significance of the findings is unknown. MIF strongly contributed to clustering of patients with LBP with MCs and controls, and might be a biomarker for MCs. Ultimately, these results may guide future research on novel treatments for this patient group.