{"doi":"10.1084/jem.20202059","title":"Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain","abstract":"Neuroinflammation is a major component in the transition to and perpetuation of neuropathic pain states. Spinal neuroinflammation involves activation of TLR4, localized to enlarged, cholesterol-enriched lipid rafts, designated here as inflammarafts. Conditional deletion of cholesterol transporters ABCA1 and ABCG1 in microglia, leading to inflammaraft formation, induced tactile allodynia in naive mice. The apoA-I binding protein (AIBP) facilitated cholesterol depletion from inflammarafts and reversed neuropathic pain in a model of chemotherapy-induced peripheral neuropathy (CIPN) in wild-type mice, but AIBP failed to reverse allodynia in mice with ABCA1/ABCG1-deficient microglia, suggesting a cholesterol-dependent mechanism. An AIBP mutant lacking the TLR4-binding domain did not bind microglia or reverse CIPN allodynia. The long-lasting therapeutic effect of a single AIBP dose in CIPN was associated with anti-inflammatory and cholesterol metabolism reprogramming and reduced accumulation of lipid droplets in microglia. These results suggest a cholesterol-driven mechanism of regulation of neuropathic pain by controlling the TLR4 inflammarafts and gene expression program in microglia and blocking the perpetuation of neuroinflammation.","journal":"The Journal of Experimental Medicine","year":2021,"id":149583,"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":104,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326177,"name":"Soo‐Ho Choi","orcid":"0000-0003-1152-1509","position":1,"is_corresponding":false},{"id":636270,"name":"Luciano dos Santos Aggum Capettini","orcid":"0000-0002-6487-9558","position":2,"is_corresponding":false},{"id":326473,"name":"Yining Xia","orcid":"0000-0003-1854-8050","position":3,"is_corresponding":false},{"id":530253,"name":"Ayelet Gonen","orcid":"0000-0001-9309-3020","position":4,"is_corresponding":false},{"id":636271,"name":"Colin Agatisa-Boyle","orcid":"0000-0002-1210-8356","position":5,"is_corresponding":false},{"id":254290,"name":"Lauriane Delay","orcid":"0000-0002-5466-9856","position":6,"is_corresponding":false},{"id":254289,"name":"Gilson Gonçalves dos Santos","orcid":"0000-0002-2704-3006","position":7,"is_corresponding":false},{"id":367181,"name":"Glaucilene Ferreira Catroli","orcid":"0000-0002-9026-176X","position":8,"is_corresponding":false},{"id":326474,"name":"Jungsu Kim","orcid":"0000-0002-7671-7089","position":9,"is_corresponding":false},{"id":636272,"name":"Jenny W. Lu","orcid":"0000-0001-5245-9989","position":10,"is_corresponding":false},{"id":636273,"name":"Benjamin P. Saylor","orcid":"0000-0003-1771-5291","position":11,"is_corresponding":false},{"id":324393,"name":"Holger Winkels","orcid":"0000-0003-1333-2031","position":12,"is_corresponding":false},{"id":636274,"name":"Christopher P. Durant","orcid":"0000-0003-1374-8141","position":13,"is_corresponding":false},{"id":490441,"name":"Yanal Ghosheh","orcid":"0000-0002-3733-2098","position":14,"is_corresponding":false},{"id":636275,"name":"Graham Beaton","orcid":"0000-0002-7705-1952","position":15,"is_corresponding":false},{"id":324398,"name":"Klaus Ley","orcid":"0000-0001-9339-3672","position":16,"is_corresponding":false},{"id":354098,"name":"Irina Kufareva","orcid":"0000-0001-9083-7039","position":17,"is_corresponding":false},{"id":256873,"name":"Maripat Corr","orcid":null,"position":18,"is_corresponding":false},{"id":254291,"name":"Tony L. Yaksh","orcid":"0000-0003-4297-536X","position":19,"is_corresponding":false},{"id":264535,"name":"Yury I. Miller","orcid":"0000-0003-0521-7690","position":20,"is_corresponding":false},{"id":636269,"name":"Juliana M. Navia‐Pelaez","orcid":"0000-0001-5709-339X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:42:56.251607Z","pmid":"33970188","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":[]}