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

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• Microglia are central nervous system immune cells that amplify pathological processes.
• Spinal microglial activation post-peripheral nerve injury (PNI) is crucial for neuropathic pain development.
• Transcription factors controlling microglial activation in neuropathic pain remain poorly understood.

Purpose of the Study:

• To investigate the role of MafB, a microglial transcription factor, in neuropathic pain.
• To elucidate the mechanisms by which MafB contributes to PNI-induced pain.

Main Methods:

• Utilized a mouse model of peripheral nerve injury (PNI).
• Assessed MafB expression in spinal cord microglia and neurons.
• Manipulated MafB and microRNA-152 (mir-152) levels via intrathecal administration (siRNA, mimic).
• Employed heterozygous Mafb deficient and conditional Mafb knockout mice.
• Performed microglial transfer experiments.

Main Results:

• PNI significantly increased MafB expression in spinal microglia.
• PNI decreased spinal mir-152, which targets MafB.
• Intrathecal mir-152 mimic suppressed neuropathic pain development.
• Reduced MafB expression (heterozygous deficiency or siRNA) alleviated PNI-induced hypersensitivity.
• MafB-deficient microglia transfer did not induce hypersensitivity.
• Conditional Mafb knockout mice showed no neuropathic pain after PNI.

Conclusions:

• MafB is a critical mediator of PNI-induced spinal microglial activation.
• MafB plays a key role in the development of neuropathic pain.
• Targeting MafB represents a potential therapeutic strategy for neuropathic pain.