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.
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This signature evokes the reactive microglia phenotype described in a mouse peripheral nerve injury model that is driven at least in part by IRF8 and MafB.
“This signature evokes the reactive microglia phenotype described in a mouse model of PNI that is driven, at least in part, by IRF827 and MafB42.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [42]
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Self-citation
- Authors
- Tozaki‐Saitoh, H., Masuda, J., Kawada, R., Kojima, C., Yoneda, S., Masuda, T., Inoue, K., & Tsuda, M.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Tozaki‐Saitoh, Hidetoshi
- Tsuda, Makoto
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2018-11-28
- Volume
- 67
- Issue
- 4
- Pages
- 729-740
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2903196953
- Cited by
- 52
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 6
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (KAKENHI JP25117013, JP23229008, JP15H02522, JP25460721)
- Japan Agency for Medical Research and Development (Research Project on Elucidation of Chronic Pain)
- Core Research for Evolutional Science and Technology (JP18gm0910006)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- MAFB, microglial activation, neuropathic pain, peripheral nerve injury, miR-152, microRNA, spinal cord, mechanical hypersensitivity, transcription factors, microglia, siRNA knockdown
- MeSH terms
- Animals, Calcium-Binding Proteins, Cells, Cultured, Disease Models, Animal, Embryo, Mammalian, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hyperalgesia, Male, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Neuralgia, Phosphopyruvate Hydratase, RNA, Messenger, Spinal Cord, Pain Threshold, Microglia, RNA, Small Interfering, CD11b Antigen, Green Fluorescent Proteins, MafB Transcription Factor, Mice
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