The role of microRNAs in maintaining low-grade inflammation in patients with discogenic back pain and comorbid sleep disorders

Chronic discogenic back pain and comorbid sleep disorders (insomnia) are a pressing and difficult-to-treat condition in the practice of neurologist. The development of this comorbidity is thought to involve common pathogenetic pathways, but the definitive connecting “bridges” have not been fully established. A growing number of recent studies focus on the phenomenon of low-grade inflammation (LGI), which underlies both the progression of intervertebral disc degeneration and insomnia. Since there are no validated, specific, and sensitive methods for assessing LGI in clinical neurology, the development of promising diagnostic panels is necessary. Signatures of small non-coding ribonucleic acids (microRNAs) represent one such promising panel, as preclinical studies have demonstrated their involvement in the epigenetic control of LGI. The influence of microRNAs on sustaining LGI, neuroplasticity, and circadian dysfunction has been established. The aim of this review is to update neurologists’ knowledge on the role of microRNAs (via the connecting “bridge” of LGI) in the pathogenesis of chronic pain syndrome associated with insomnia in patients with intervertebral disc degeneration (IVDD), and to assess their diagnostic potential. A search for publications was conducted in the PubMed, Springer, Research Gate, Google Scholar, Cochrane, and e-Library databases for the period 2016–2026 using the keywords: inflammation, lowgrade inflammation, intervertebral disc degeneration, discogenic pain syndrome, neuropathic pain syndrome, comorbidity, insomnia, diagnosis, epigenetics, microRNAs. The analysis includes original preclinical and clinical studies, as well as systematic reviews. The review summarizes data on more than 40 microRNAs involved in the regulation of key inflammatory pathways (NF-κB, NLRP3 inflammasome, etc.) and circadian genes (PER, BMAL1, CLOCK, etc.) in intervertebral disc (IVD) cells and the central nervous system. A signature of the most promising candidates (miR-29a, miR-132, miR-155, miR-34a-5p, and the let-7 family), which are simultaneously involved in the regulation of LGI, pain signaling, and circadian rhythms, has been identified. The expression levels of certain microRNAs (miR-340-5p, miR-494) have been shown to correlate with the severity of IVDD on MRI and may serve as sensitive epigenetic biomarkers. MicroRNAs are promising epigenetic biomarkers and therapeutic targets for personalized therapy of discogenic back pain and insomnia in IVDD. Further translational and validation clinical studies are required to introduce the microRNA signature into neurological practice.