{"doi":"10.1101/2022.12.20.521295","title":"Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution","abstract":"Summary Microglia contribute to the initiation of pain, however, a translationally viable approach addressing how or when to modulate these cells remains elusive. We used a targeted, inducible, genetic microglial depletion strategy at both acute and acute-to-chronic transition phases in the clinically-relevant tibial fracture/casting pain model to determine the contribution of microglia to the initiation and maintenance of pain. We observed complete resolution of pain after transient microglial depletion at the acute-to-chronic phase, which coincided with the timeframe of full repopulation of microglia. These repopulated microglia were morphologically distinct from control microglia, signifying they may exhibit a unique transcriptome. RNA sequencing of repopulated spinal cord microglia identified genes of interest using weighted gene co-expression network analysis (WGCNA). We intersected these genes with a newly-generated single nuclei microglial dataset from human spinal cord dorsal horn and identified human-relevant genes that may ultimately promote pain resolution after injury. This work presents a novel approach to gene discovery in pain and provides comprehensive datasets for the development of future microglial-targeted therapeutics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313829,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":938110,"name":"Caldwell M. Bridges","orcid":"0000-0003-1956-8950","position":1,"is_corresponding":false},{"id":369997,"name":"Amy R. Nippert","orcid":"0000-0002-7724-2513","position":2,"is_corresponding":false},{"id":818307,"name":"Meng Wang","orcid":"0000-0002-4970-8590","position":3,"is_corresponding":false},{"id":289055,"name":"Shaogen Wu","orcid":"0000-0001-5653-3357","position":4,"is_corresponding":false},{"id":820831,"name":"Thomas E. Forman","orcid":"0000-0002-8912-3503","position":5,"is_corresponding":false},{"id":494377,"name":"Elena S. Haight","orcid":"0000-0002-3463-0591","position":6,"is_corresponding":false},{"id":494376,"name":"Nolan A. Huck","orcid":"0000-0001-8164-6695","position":7,"is_corresponding":false},{"id":617721,"name":"Sabrina F. Bond","orcid":"0000-0002-5628-145X","position":8,"is_corresponding":false},{"id":938109,"name":"Claire E. Jordan","orcid":"0000-0001-7310-1302","position":9,"is_corresponding":false},{"id":1012870,"name":"Aysha S. Gardner","orcid":null,"position":10,"is_corresponding":false},{"id":348867,"name":"Ramesh V. Nair","orcid":"0000-0002-1323-3247","position":11,"is_corresponding":false},{"id":267285,"name":"Vivianne L. Tawfik","orcid":"0000-0002-4422-2014","position":12,"is_corresponding":false},{"id":938108,"name":"Lauren J. Donovan","orcid":"0000-0002-5622-7402","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"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":[]}