Related Experiment Video
Updated: Aug 6, 2026
Modeling Multiple Sclerosis in the Two Sexes: MOG35-55-Induced Experimental Autoimmune Encephalomyelitis
Published on: October 13, 2023
4E-BP1-dependent translation in microglia controls mechanical hypersensitivity in male and female mice
Kevin C Lister1, Calvin Wong1, Weihua Cai1
1Department of Anesthesia and.
Abstract:
Spinal microglia play a pivotal role in the development of neuropathic pain. Peripheral nerve injury induces changes in the transcriptional profile of microglia, including increased expression of components of the translational machinery. Whether microglial protein synthesis is stimulated following nerve injury and has a functional role in mediating pain hypersensitivity is unknown. Here, we show that nascent protein synthesis is upregulated in spinal microglia following peripheral nerve injury in both male and female mice. Stimulating mRNA translation in microglia by selectively ablating the translational repressor eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) promoted the transition of microglia to a reactive state and induced mechanical hypersensitivity in both sexes, whereas spontaneous pain was increased only in males. Conversely, inhibiting microglial translation by expressing a mutant form of 4E-BP1 in microglia attenuated their activation following peripheral nerve injury and alleviated neuropathic pain in both sexes. Thus, stimulating 4E-BP1-dependent translation promotes microglial reactivity and mechanical hypersensitivity, whereas inhibiting it alleviates neuropathic pain.
Insights
Spinal microglia protein synthesis drives neuropathic pain. Inhibiting translation in these cells alleviates pain hypersensitivity, highlighting a therapeutic target for nerve injury pain.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Spinal microglia are crucial in neuropathic pain development.
- Peripheral nerve injury alters microglial gene expression, including protein synthesis machinery.
- The role of microglial protein synthesis in pain hypersensitivity remains unclear.
Purpose of the Study:
- To investigate if microglial protein synthesis is upregulated after nerve injury.
- To determine the functional role of microglial translation in neuropathic pain.
- To explore the impact of modulating eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) on microglial activity and pain.
Main Methods:
- Assessed nascent protein synthesis in spinal microglia post-peripheral nerve injury in male and female mice.
- Genetically manipulated microglial 4E-BP1 levels to stimulate or inhibit mRNA translation.
- Evaluated microglial activation states and pain behaviors (mechanical hypersensitivity, spontaneous pain).
Main Results:
- Nascent protein synthesis was upregulated in spinal microglia following nerve injury in both sexes.
- Ablating 4E-BP1 enhanced microglial reactivity and mechanical hypersensitivity.
- Inhibiting microglial translation via mutant 4E-BP1 attenuated microglial activation and alleviated neuropathic pain.
Conclusions:
- Upregulated microglial translation, dependent on 4E-BP1, promotes reactivity and mechanical hypersensitivity.
- Inhibition of microglial translation offers a potential therapeutic strategy for neuropathic pain.
- Microglial protein synthesis is a key mediator of neuropathic pain development.
