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Alteration of microRNA Expression Associated with Chronic Back Pain in Patients with Intervertebral Disc
Azamat V Ashkhotov1,2, Natalia A Shnayder1,3, Vera V Trefilova1
1Institute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia.
Abstract:
Chronic back pain (CBP) associated with intervertebral disc degeneration (IVDD) is a leading cause of medical consultations, decreased quality of life, and temporary and permanent disability. The mechanisms of CBP development and persistence in patients with IVDD have been studied for many years, but this issue remains far from resolved. The search for predictive biomarkers that could help identify patients with IVDD at high risk for CBP continues. In recent decades, research has shown increasing interest in identifying epigenetic biomarkers for this disorder. to summarize the results of preclinical and clinical studies on the role of microRNAs (miRs) as epigenetic biomarkers of the development and progression of CBP in patients with IVDD. English-language articles; original experimental (preclinical) studies; original clinical study; assessment of changes in systemic (in the blood) and/or local (in the intervertebral disk (IVD)) levels of miR expression in IVDD, either independently or in comparison with healthy controls; and studies that were completed and the results of which were published. PubMed, Springer, Google Scholar, Scopus, Oxford Press, Cochrane, and e-Library databases. Charting for this scoping review involved developing a data extraction form to summarize extracts and organize data from included studies. This was an iterative process where the charting tables and figures may be refined as the review progresses. 126 studies were analyzed in detail, focusing on their study designs and comparing changes in miR expression in animal models of IVDD and in patients with IVDD compared to healthy controls. During the preparation of this scoping review and upon subsequent detailed review of the original publications, it turned out that the results of one study were not justified by the authors due to identified technological problems (the article was withdrawn by the editorial board of the journal). Therefore, we excluded the results of this study from the subsequent analysis. As a result, this section summarizes the results of 60 preclinical and 65 clinical studies. Some miRs (e.g., miR-21 and miR-132) are associated with the regulation of inflammatory pathways that contribute to increased degradation of IVD extracellular matrix and enhanced nociceptive signaling through various mechanisms, contributing to the progression of CBP. Other miRs (e.g., miR-145 and miR-223) exert protective effects, enhance regenerative potential, and alleviate CBP. Despite the promising results of these studies, there are limitations in the use of miRs as perspective epigenetic biomarkers of CBP in patients with IVDD because the pattern of potentially predictive and protective miRs in relation to the mechanisms of CBP formation and progression in IVDD has not yet been sufficiently studied. The results of some preclinical and clinical studies are contradictory. Further research is needed to clarify the role of miR signatures in animal models and clinical trials on IVDD-specific CBP.
Insights
MicroRNAs (miRs) show potential as epigenetic biomarkers for chronic back pain (CBP) in intervertebral disc degeneration (IVDD). Some miRs promote IVDD progression, while others offer protective effects, but further research is needed to clarify their roles.
Area of Science:
- Biomarkers
- Epigenetics
- MicroRNAs
Background:
- Chronic back pain (CBP) linked to intervertebral disc degeneration (IVDD) significantly impacts quality of life and disability.
- Identifying predictive biomarkers for CBP in IVDD patients is crucial for effective management.
- Epigenetic biomarkers, particularly microRNAs (miRs), are gaining attention for their potential role in IVDD-associated CBP.
Purpose of the Study:
- To systematically review and summarize preclinical and clinical studies on microRNAs (miRs) as epigenetic biomarkers for CBP in patients with IVDD.
- To explore the association between miR expression levels and the development and progression of CBP in IVDD.
- To identify specific miRs that may serve as predictive or protective biomarkers for CBP in IVDD.
Main Methods:
- A comprehensive literature search was conducted across multiple databases (PubMed, Springer, Google Scholar, Scopus, Oxford Press, Cochrane, e-Library).
- Included studies were original experimental (preclinical) and clinical research assessing miR expression in IVDD patients and/or animal models compared to controls.
- Data from 125 studies (60 preclinical, 65 clinical) were analyzed, focusing on miR expression changes in systemic and local tissues.
Main Results:
- Certain miRs (e.g., miR-21, miR-132) are implicated in promoting IVDD progression by regulating inflammatory pathways and extracellular matrix degradation.
- Other miRs (e.g., miR-145, miR-223) demonstrate protective effects, potentially enhancing regenerative capacity and alleviating CBP.
- Contradictory findings exist, and the precise role of miR signatures in CBP development and progression within IVDD remains incompletely understood.
Conclusions:
- MicroRNAs show promise as epigenetic biomarkers for CBP in IVDD, with some miRs linked to disease progression and others to protective effects.
- Limitations exist due to insufficient research on the comprehensive pattern of miRs and their relation to CBP mechanisms in IVDD.
- Further rigorous research, including animal models and clinical trials, is essential to elucidate the role of miR signatures and validate their clinical utility for IVDD-associated CBP.
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