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Modulation of central nervous system–specific microRNA‐124a alters the inflammatory response in the formalin test in mice

: Kynast, K.; Russe, O.; Möser, C.; Geisslinger, G.; Niederberger, E.


Pain 154 (2012), Nr.3, S.368-376
ISSN: 0304-3959
ISSN: 1872-6623
Fraunhofer IME ()

microRNAs (miRNAs) are small noncoding RNAs that have been linked to a number of disease‐related signal transduction pathways. Several studies indicate that they are also involved in nociception. It is not clear, however, which miRNAs are important and which genes are modulated by miRNA‐associated mechanisms. This study focuses on the regulation and function of the central nervous system (CNS)–specific miRNA‐124a in the spinal cord of mice in a formalin model of inflammatory nociception. miRNA‐124a is constitutively expressed in the spinal cord of mice, particularly in neurons of the dorsal horn. Peripheral noxious stimulation with formalin led to significant down‐regulation of its expression. Knock‐down of miRNA‐124a by intravenous administration of a specific miRNA‐124a inhibitor further increased the nociceptive behavior associated with an upregulation of the pain‐relevant miRNA‐124a target MeCP2 and proinflammatory marker genes. In contrast, administration of a miRNA‐124a mimic counteracted these effects and decreased nociception by down‐regulation of the target gene. In conclusion, our results indicate that miRNA‐124a is involved in inflammatory nociception by regulation of relevant target proteins and might therefore constitute a novel target for anti‐inflammatory therapy.