MicroRNA-223 demonstrated experimentally in exosome-like vesicles is associated with decreased risk of persistent pain after lumbar disc herniation

• Published in: Journal of translational medicine 2017-05, Vol.15 (1), p.89-89, Article 89
• Main Authors: Moen, Aurora, Jacobsen, Daniel, Phuyal, Santosh, Legfeldt, Anna, Haugen, Fred, Røe, Cecilie, Gjerstad, Johannes
• Format: Article
• Language: English
• Subjects: Adult; Animals; Cell growth; Disc herniation; Electrodes; Electron microscopy; Enzyme-linked immunosorbent assay; Exosomes - metabolism; Exosomes - ultrastructure; Experiments; Female; Fibromyalgia; Gene expression; Health risks; Humans; Immune response; Inflammation; Interleukin 6; Intervertebral Disc Displacement - complications; Intervertebral Disc Displacement - pathology; Intervertebral Disc Displacement - physiopathology; Intervertebral discs; Lumbar radicular pain; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Male; microRNA-223; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-223; miRNA; Nanoparticles; Neurons; Non-coding RNA; Nucleus pulposus; Pain; Pain - etiology; Pain - genetics; Pain perception; Rats, Inbred Lew; Recovery of Function; Rheumatoid arthritis; Risk Factors; Signal transduction; Smoking; Spinal cord; Up-Regulation - genetics; Vertebrae; Vesicles; Visual Analog Scale; Young Adult
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-017-1194-8

Previous findings have demonstrated that lumbar radicular pain after disc herniation may be associated with up-regulation of inflammatory mediators. In the present study we examined the possible role of extracellular microRNAs (miRs) in this process. Single unit recordings, isolation of exosome-like vesicles, electron microscopy, nanoparticle tracking analysis, western blot analysis and qPCR were used in rats to demonstrate the effect of nucleus pulposus (NP) applied onto the dorsal nerve roots. ELISA and qPCR were used to measure the level of circulating IL-6 and miRs in a 1-year observational study in patients after disc herniation. In the rats, enhanced spinal cord nociceptive responses were displayed after NP applied onto the dorsal nerve roots. An increased release of small non-coding RNAs, including miR-223, miR-760 and miR-145, from NP in exosome-like vesicles was demonstrated. In particular, the NP expression of miR-223, which inhibited the nociceptive spinal signalling, was increased. In the patients, increased extracellular miR-223 was also verified in the acute phase after disc herniation. The increased miR-223 expression was, however, only observed in those who recovered (sex, age and smoking were included as covariates). Our findings suggest that miR-223, which can be released from the NP after disc herniation, attenuates the neuronal activity in the pain pathways. Dysregulation of miR-223 may predict chronic lumbar radicular pain. Trial registration/ethics REK 2014/1725.