GSE265957 Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain

Contributors : Kevin Lister ; Sonali Uttam ; Marc Pairsien ; Arkady KhoutorskySeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusSensitization of spinal nociceptive circuits plays a cardinal role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory neurons exhibited greater changes in translation after peripheral nerve injury compared to excitatory neurons. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV + ) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV + neurons decreased their intrinsic excitability and spiking activity, whereas reducing translation in spinal PV + neurons prevented the nerve injury-induced decrease in excitability. Thus, translational control mechanisms in the spinal cord, primarily in inhibitory neurons, play a criti...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Mus musculus Source Type: research