Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development

Abstract

Microglia, which are pathological effectors and amplifiers in the central nervous system, undergo various forms of activation. A well‐studied microglial‐induced pathological paradigm, spinal microglial activation following peripheral nerve injury (PNI), is a key event for the development of neuropathic pain but the transcription factors contributing to microglial activation are less understood. Herein, we demonstrate that MafB, a dominant transcriptional regulator of mature microglia, is involved in the pathology of a mouse model of neuropathic pain. PNI caused a rapid and marked increase of MafB expression selectively in spinal microglia but not in neurons. We also found that the microRNA mir‐152 in the spinal cord which targets MafB expression decreased after PNI, and intrathecal administration of mir‐152 mimic suppressed the development of neuropathic pain. Reduced MafB expression using heterozygous Mafb deficient mice and by intrathecal administration of siRNA alleviated the development of PNI‐induced mechanical hypersensitivity. Furthermore, we found that intrathecal transfer of Mafb deficient microglia did not induce mechanical hypersensitivity and that conditional Mafb knockout mice did not develop neuropathic pain after PNI. We propose that MafB is a key mediator of the PNI‐induced phenotypic alteration of spinal microglia and neuropathic pain development.

Microglia-Mediated Regulation of Neuropathic Pain: Molecular and Cellular Mechanisms

“…66) IRF8 directly regulates other members of the IRF family such as IRF1 and IRF5. 67,68) IRF5 was shown to bind to the putative promoter region of P2X4R and enhance its expression. 67) Indeed, a deficiency of IRF5 suppressed the PNI-induced spinal P2X4R upregulation and neuropathic allodynia.…”

Spatiotemporal Expression of SphK1 and S1PR2 in the Hippocampus of Pilocarpine Rat Model and the Epileptic Foci of Temporal Lobe Epilepsy

“…Immunofluorescence quantification was performed using Image J software, following the Image J User Guide 1 (NIH, Bethesda, MD). For calculating GFAP-positive cells, SphK1-positive cells, and S1PR2 -positive cells, five brain slices of each sample were analyzed in histological analysis using the Image J cell counting plugin tool ( Chen et al, 2019 ; Tozaki-Saitoh et al, 2019 ).…”

Role of MafB in macrophages

“…MafB is a target of miR-155, and miR-155 induces inflammatory macrophages [29,36]. In contrast, miR-152 is reported to target MafB in microglia [72]. MafB is similarly regulated by various signals, including lipid metabolism, immunological regulators, and microRNAs (Fig.…”