Transcription factor MafB contributes to activation of spinal microglia and neuropathic pain after peripheral nerve injury

Abstract

Microglia, which are pathological effectors and amplifiers in the central nervous system, undergo various forms of activation. Activation of spinal microglial 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.Here, we demonstrate that MafB, a dominant transcriptional regulator of mature microglia, is involved in the pathology of neuropathic pain. PNI caused an increase of MafB expression selectively in spinal microglia. We measured expression of mir-152, a microRNA targeting MafB, and found a transient decrease in its expression in the spinal cord after PNI. Moreover, intrathecal administration of mir-152 mimic suppressed the development of neuropathic pain. Reduced MafB expression using heterozygous Mafb-deficient mice alleviated 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. We propose that MafB is a key mediator of the PNI-induced phenotypic alteration of spinal microglia and neuropathic pain development.