Expression of miRNA-124a in CD4 Cells Reflects Response to a Multidisciplinary Treatment Program in Patients With Chronic Low Back Pain

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Abstract

Study Design.

A prospective evaluation of microRNA (miRNA) expression in patients with chronic low back pain (CLBP).

Objective.

The aim of this study was to evaluate whether pain- and T cell-related miRNAs are differentially expressed in CLBP when compared with healthy volunteers and whether these miRNAs may distinguish between responders and nonresponders to a multidisciplinary treatment program.

Summary of Background Data.

CLBP is a common health problem worldwide. Multidisciplinary pain treatment programs have been proven as an effective treatment option. miRNAs are known to be important mediators of gene regulation in various processes, including pathophysiology of pain. The expression of miRNAs in CLBP and changes due to a multidisciplinary treatment programs are still unknown.

Methods.

Thirty-four patients with CLBP were enrolled (46.5 ± 12.7 yrs). CLBP was defined as low back pain with an average intensity of numerical rating scale (NRS) ≥3 during the last 4 weeks, persisting longer than 6 months, and not attributable to a recognized specific pathological condition. Expression of pain- and T cell-related miRNAs in human CD4+ cells were determined using TaqMan assays and RealTime PCR. MiRNA expression in patients with CLBP was compared with the expression in healthy volunteers before a multidisciplinary treatment program started. The multidisciplinary outpatient program (4 weeks, 5 days a week, 8 h per day) is a clinically established outpatient program and comprises medical (examination, education), physical (exercise), work-related, and psychological therapy components. After the program, differentially expressed miRNAs in CLBP (before treatment) were analyzed once more. Expression of these miRNAs in patients who respond to the treatment (n = 14) was compared with those who did not respond (n = 20). Response to therapy was defined as reduction of pain of ≥50% (NRS) from baseline.

Results.

MiRNA-124a (patients: 0.79 ± 0.63 vs. healthy volunteers: 0.30 ± 0.16; P < 0.001), miRNA-150 (patients: 0.75 ± 0.21 vs. healthy volunteers: 0.56 ± 0.20; P = 0.025), and miRNA-155 (patients: 0.55 ± 0.14 vs. healthy volunteers: 0.38 ± 0.16; P = 0.017) were significantly upregulated in CLBP patients when compared with healthy volunteers. After the multidisciplinary treatment program, patients who respond to the treatment showed only an increase of miRNA-124a expression (before treatment: 0.54 ± 0.26 vs. after treatment: 1.05 ± 0.56, P = 0.007).

Conclusion.

MiRNA-124a upregulation is associated with therapy response in a multidisciplinary treatment programs and might help to identify more specific and mechanism-based treatment strategies for CLBP.

Conclusion.

Level of Evidence: 3

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