{"doi":"10.1126/sciadv.adh9603","title":"4E-BP1–dependent translation in nociceptors controls mechanical hypersensitivity via TRIM32/type I interferon signaling","abstract":"Activation of the mechanistic target of rapamycin complex 1 (mTORC1) contributes to the development of chronic pain. However, the specific mechanisms by which mTORC1 causes hypersensitivity remain elusive. The eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) is a key mTORC1 downstream effector that represses translation initiation. Here, we show that nociceptor-specific deletion of 4E-BP1, mimicking activation of mTORC1-dependent translation, is sufficient to cause mechanical hypersensitivity. Using translating ribosome affinity purification in nociceptors lacking 4E-BP1, we identified a pronounced translational up-regulation of tripartite motif-containing protein 32 (TRIM32), an E3 ubiquitin ligase that promotes interferon signaling. Down-regulation of TRIM32 in nociceptors or blocking type I interferon signaling reversed the mechanical hypersensitivity in mice lacking 4E-BP1. Furthermore, nociceptor-specific ablation of TRIM32 alleviated mechanical hypersensitivity caused by tissue inflammation. These results show that mTORC1 in nociceptors promotes hypersensitivity via 4E-BP1-dependent up-regulation of TRIM32/interferon signaling and identify TRIM32 as a therapeutic target in inflammatory pain.","journal":"Science Advances","year":2023,"id":328766,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":457554,"name":"Diana Tavares‐Ferreira","orcid":"0000-0003-0986-3630","position":1,"is_corresponding":false},{"id":1050764,"name":"Carolina Thörn Pérez","orcid":"0000-0002-3480-8599","position":2,"is_corresponding":false},{"id":1050765,"name":"Behrang Sharif","orcid":"0000-0002-6451-2596","position":3,"is_corresponding":false},{"id":1051346,"name":"Sonali Uttam","orcid":null,"position":4,"is_corresponding":false},{"id":1050766,"name":"Mehdi Amiri","orcid":"0000-0002-8646-2649","position":5,"is_corresponding":false},{"id":1050767,"name":"Kevin C. Lister","orcid":"0000-0001-7645-3928","position":6,"is_corresponding":false},{"id":913586,"name":"Mehdi Hooshmandi","orcid":"0000-0003-1592-8664","position":7,"is_corresponding":false},{"id":1050768,"name":"Vivienne Nguyen","orcid":"0009-0003-1677-5740","position":8,"is_corresponding":false},{"id":567000,"name":"Philippe Séguéla","orcid":"0000-0001-7537-4427","position":9,"is_corresponding":false},{"id":17875,"name":"Nahum Sonenberg","orcid":"0000-0002-4707-8759","position":10,"is_corresponding":false},{"id":257966,"name":"Theodore J. Price","orcid":"0000-0002-6971-6221","position":11,"is_corresponding":false},{"id":597560,"name":"Christos G. Gkogkas","orcid":"0000-0001-6281-3419","position":12,"is_corresponding":false},{"id":260659,"name":"Arkady Khoutorsky","orcid":"0000-0003-3846-8728","position":13,"is_corresponding":false},{"id":913593,"name":"Calvin Wong","orcid":"0000-0001-7728-3035","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37922363","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}