Figure 1.

MiRNAs regulate several mechanisms of postoperative pain. Postoperative pain results from an accumulation of multiple sources, including central and peripheral nervous systems and inflammatory contributions. At several of these sites, miRNAs have demonstrated important roles in regulating mechanisms that can both promote (highlighted in red) and limit (highlighted in blue) pain. In the setting of somatic pain, such as pain occurring at the incisional site, miRNAs play regulatory roles in the central nervous system, such as miR-150 targeting of TLR5 and miR-93 targeting of STAT3, that result in decreased proinflammatory cytokine expression. In a similar fashion, miRNAs also regulate proinflammatory signaling from immune cells that contribute to inflammatory pain. These miRNAs include miR-15a and miR-21, which promote inflammation, and miR-124, which has an inhibitory role. Visceral pain has also been shown to be regulated by miRNAs in both positive and negative manners. At the level of sensory nerves, genetic studies and experimental siRNA-based therapies have implicated sodium and potassium ion channels as potential targets for analgesic treatments. Altogether, there is a growing accumulation of evidence implicating miRNA-mediated regulation of pain. COX indicates cyclooxygenase; DRG, dorsal root ganglia; IL, interleukin; miR, microRNA; miRNA, microribonucleic acid; NAV, voltage-gated sodium channel; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; NPY, neuropeptide Y; PLAA, phospholipase A2 activating protein; siRNA, small interference RNA; STAT3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TNF, tumor necrosis factor; TRPV, transient receptor potential cation channel subfamily V member.