4E-BP1-dependent translation in microglia controls mechanical hypersensitivity

Spinal microglia play a pivotal role in the development of neuropathic pain. Peripheral nerve injuryinduces changes in the transcriptional profile of microglia, including increased expression ofcomponents of translational machinery. Whether microglial protein synthesis is stimulated followingnerve injury and has a functional role in mediating pain hypersensitivity is unknown. Here, we showthat nascent protein synthesis is upregulated in spinal microglia following peripheral nerve injury.Stimulating mRNA translation in microglia, via selective ablation of the translational repressor,eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), promoted the transition of microglia to areactive state and induced mechanical hypersensitivity. Conversely, inhibiting microglial translation byexpressing mutant 4E-BP1 in microglia attenuated their peripheral nerve injury-induced activation andalleviated neuropathic pain. Thus, the stimulation of 4E-BP1-dependent translation promotes microgliareactivity and mechanical hypersensitivity, whereas its inhibition alleviates neuropathic pain.