The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.

Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.

An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).

Introduction. Intervertebral disc (IVD) degeneration is defined as a multifactorial degenerative disease of the spine, starting from the structures of the nucleus pulposus of the IVD, spreading to the fibrous ring and other elements of the spinal motion segment. Unlike natural aging, a pathological degenerative process that occurs in IVDs as a result of the additive effect of genetic predisposition and external environmental factors leads to the formation of chronic back pain and reduces the patient’s quality of life. Despite many years of studying the problem of the pathogenesis of IVD degeneration, it is far from being resolved, which encourages us to further study the pathogenetic mechanisms of the development of this pathology.Aim. To update the knowledge of practicing neurologists about the results of modern studies of the leading mechanisms of development of IVD degeneration in humans and their role in the development of promising biomarkers of this pathology and new strategies for pathogenetic therapy.Materials and methods. A search and analysis of publications was carried out in Russian-language (e-Library) and Englishlanguage databases (PubMed, Oxford Press, Clinical Keys, Springer, Elsevier, Google Scholar). Search depth – 5 years (2018–2023).Results. The analyzed and generalized results of studies of the molecular mechanisms influencing the development and progression of this pathology are presented. The leading pathogenetic mechanisms for the development of IVD degeneration, such as oxidative stress and the NO system, cytokine imbalance, increased activity of matrix metalloproteinases, dysfunction of fibrillar collagens and proteoglycan, as well as their relationship with each other, were considered.Conclusion. The review provides a broader look at the pathogenetic mechanisms of IVD degeneration, which makes it possible to set new goals for future development of promising therapeutic strategies.

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.

The purpose of this review is to update the knowledge of neurologist doctors about the role of pro-inflammatory cytokines in the evelopment and chronicity of discogenic pain syndrome in patients with intervertebral disc degeneration. Keywords: cytokines; cytokine status; disk degeneration; biomarker; chronic inflammation, discogenic pain syndrome.