Suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia

Abstract

Introduction: The polarization state of microglia affects the progress of neuropathic pain. MiR-155 modulates polarization of microglia, while its role in neuropathic pain has not been well studied. Material and methods: We separately used lipopolysaccharide (LPS) and interleukin 4 (IL-4) for constructing an M1/M2 polarization model in BV-2 cells. The levels of CD86, iNOS, CD206, Arg and miR-155 were measured by western blot or qRT-PCR, as needed. Subsequently, BV-2 cells were transfected with miR-155 mimics or inhibitor to explore the effects of miR-155 on polarization states. We also constructed a neuropathic pain model by applying spinal nerve ligation (SNL) in Wistar rats with miR-155 agomir or antagomir injection. The withdrawal threshold was measured by Von Frey fibre needle. The levels of interleukin 1β (IL-1β), tumour necrosis factor α (TNF-α) and the proportion of M1-polarized microglia in primary microglia from rats were measured by ELISA and flow cytometry. Results: LPS induced M1 polarization in BV-2 cells with increasing of CD86, iNOS and miR-155, while IL-4 induced M2 polarization in BV-2 cells with increasing of CD206, Arg and decreasing of miR-155. MiR-155 mimics upregulated CD86 and downregulated CD206, whereas miR-155 inhibitor downregulated CD86 and upregulated CD206. MiR-155 antagomir increased the withdrawal threshold, decreased the production of IL-1β, TNF-α and the proportion of M1-polarized microglia in primary microglia. Conclusions: Results demonstrate that suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia. Our findings provide a new perspective to understand the function of miR-155 in microglia.