Macrophage migration inhibitory factor: a potential biomarker for chronic low back pain in patients with Modic changes

Abstract

BackgroundLow 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.ObjectivesTo identify possible serum biomarkers for LBP in patients with MCs.MethodsIn 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).ResultsAnalyses 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).ConclusionsThese 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.

Fatty infiltration of the erector spinae at the upper lumbar spine could be a landmark for low back pain

“…7,8 Intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles were considered as the possible origins of LBP. [9][10][11][12][13][14][15][16][17] However, patients with LBP and asymptomatic subjects did not differ in prevalence of IVDD and Modic changes. 18,19 Even though parasinal muscles are the main stabilizers of the lumber spine, most of the previous studies did not focus on paraspinal muscles.…”

“…Spine studies have focused on IVDD and Modic changes rather than paraspinal muscles until the recent decade. [12][13][14][15][16][17][18][19]21 It has been reported that multifidus could be the source of LBP in symptomatic subjects. 29 However, studies comparing the symptomatic and matched asymptomatic subjects were rare.…”

“…Spine studies have focused on IVDD and Modic changes rather than paraspinal muscles until the recent decade 12–19,21 . It has been reported that multifidus could be the source of LBP in symptomatic subjects 29 .…”

“…Recent studies focused on the pathogenesis of LBP 7,8 . Intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles were considered as the possible origins of LBP 9–17 . However, patients with LBP and asymptomatic subjects did not differ in prevalence of IVDD and Modic changes 18,19 .…”

Biomarkers for intervertebral disc and associated back pain: From diagnosis to disease prognosis and personalized treatment

“…Systemic inflammatory mediators from patients with vertebral endplate bone marrow lesions visualized on MRI as Modic changes (MCs) were analyzed. The results suggest MIF was strongly expressed in LBP patients with MC 111 . In a similar study, Karppinen et al screened diverse panels of biomarkers in serum of CLBP patients with MCs compared to a matched pain‐free control group 112 .…”