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Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development.
Glia. 2019 04; 67(4):729-740.GLIA

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.

Authors+Show Affiliations

Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30485546

Citation

Tozaki-Saitoh, Hidetoshi, et al. "Transcription Factor MafB Contributes to the Activation of Spinal Microglia Underlying Neuropathic Pain Development." Glia, vol. 67, no. 4, 2019, pp. 729-740.
Tozaki-Saitoh H, Masuda J, Kawada R, et al. Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. Glia. 2019;67(4):729-740.
Tozaki-Saitoh, H., Masuda, J., Kawada, R., Kojima, C., Yoneda, S., Masuda, T., Inoue, K., & Tsuda, M. (2019). Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. Glia, 67(4), 729-740. https://doi.org/10.1002/glia.23570
Tozaki-Saitoh H, et al. Transcription Factor MafB Contributes to the Activation of Spinal Microglia Underlying Neuropathic Pain Development. Glia. 2019;67(4):729-740. PubMed PMID: 30485546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. AU - Tozaki-Saitoh,Hidetoshi, AU - Masuda,Junya, AU - Kawada,Ryu, AU - Kojima,Chinami, AU - Yoneda,Sosuke, AU - Masuda,Takahiro, AU - Inoue,Kazuhide, AU - Tsuda,Makoto, Y1 - 2018/11/28/ PY - 2018/03/19/received PY - 2018/09/27/revised PY - 2018/10/25/accepted PY - 2018/11/30/pubmed PY - 2019/6/14/medline PY - 2018/11/29/entrez KW - MafB KW - microglia KW - neuropathic pain SP - 729 EP - 740 JF - Glia JO - Glia VL - 67 IS - 4 N2 - 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. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/30485546/Transcription_factor_MafB_contributes_to_the_activation_of_spinal_microglia_underlying_neuropathic_pain_development_ L2 - https://doi.org/10.1002/glia.23570 DB - PRIME DP - Unbound Medicine ER -