Pharmacological blockade of CCR5 was effective in the treatment of the development and maintenance phases of neuropathic pain. Thus, CCR5 antagonists may be potential new drugs for the treatment of neuropathic pain.

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, 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.