MiR‐223‐3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling

Abstract Background Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR‐223‐3p in mouse models of TN. Methods Infraorbital nerve chronic constriction injury (CCI‐ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR‐223‐3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI‐ION mice was measured using RT‐qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR‐223‐3p and MKNK2 was tested by a luciferase reporter assay. Results We found that miR‐223‐3p was downregulated, while MKNK2 was upregulated in TGs of CCI‐ION mice. MiR‐223‐3p overexpression by an intracerebroventricular injection of Lv‐miR‐223‐3p attenuated trigeminal neuropathic pain in CCI‐ION mice, as well as reduced the protein levels of pro‐inflammatory cytokines in TGs of CCI‐ION mice. MKNK2 was verified to be targeted by miR‐223‐3p. Additionally, miR‐223‐3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI‐ION mice to inhibit MAPK/ERK signaling. Conclusions Overall, miR‐223‐3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling