MicroRNA-based therapy in pain medicine: Current progress and future prospects

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules of 18-25 nucleotides in length that regulate gene expression involved in fundamental cell processes. The induction and chronification of pain is associated with many expressional changes in pain-related proteins. miRNA has the potential to regulate gene and protein expression associated with the induction and chronification of pain. Thus, miRNAs might have promise in therapy and as a diagnostic and prognostic biomarker in pain medicine. The application of miRNA has been an emerging field in pain research in recent years. Many studies focusing on the regulation of miRNAs under different tissue and nociceptive stimuli have been performed in recent years. In this review, we intend to introduce the most recent research in the field of miRNA related with pain medicine such as the expression and function of miRNA in different animal pain model, the challenge of application and delivery of miRNA in vivo, the potential toxic effects of miRNA and future problems in clinical application that need to be resolved. This review focuses on the results of miRNA in animal studies and the prospect for future success.

MicroRNA Biology and Pain

“…Recent reviews have cataloged the studies linking miRNAs to various pain conditions. 62,65,[69][70][71][72] Profiling studies have identified tissue-specific deregulated expression of miRNAs in DRG and spinal cord after peripheral inflammatory stimulus, 73,74 nerve injury, [74][75][76][77][78][79][80] and cancer pain. 81 Additionally, differential regulation of individual miRNAs has been observed in specific regions of the brain in acute and chronic pain models.…”

Circulating microRNA Signatures in Rodent Models of Pain

“…miRNAs are known to play an important role in many diseases [7] and their stability in bodily fluids make them highly suitable as potential biomarkers [8]. Recent reviews have catalogued the studies linking miRNAs to various pain conditions, and miRNAs likely play a role in the development of chronic pain owing to their alteration of gene expression [9][10][11][12][13][14].…”

“…Studies that attempt to pursue similar molecular biomarkers between animals and humans may provide valuable information to align preclinical studies with human outcomes. Several studies have examined miRNA expression in the dorsal root ganglion (DRG), trigeminal ganglion, and spinal cord resulting from inflammatory pain models such as complete Freund's adjuvant (CFA), capsaicin, and carrageenan, as well as neuropathic pain models such as spinal nerve ligation (SNL), spared nerve injury (SNI), chronic constriction injury, and sciatic nerve crush [9][10][11][12][13][14]. However, changes in miRNA expression in whole blood from these models have not previously been reported.…”

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…The expression and function of miRNA in different animal pain models needs to consider due to the challenge of application and delivery of miRNA in vivo, the potential toxic effects of miRNA and future problems in clinical application [74]. Furthermore, an existing model of miR-134 shows a balanced expression of MOR1 in DRGs in CFA-induced inflammatory pain, which implies that miR-134 may be a potential therapeutic target for the treatment of neuropathic pain including inflammation [75].…”