{"doi":"10.1126/sciadv.abi8834","title":"NAAA-regulated lipid signaling governs the transition from acute to chronic pain","abstract":"Chronic pain affects 1.5 billion people worldwide but remains woefully undertreated. Understanding the molecular events leading to its emergence is necessary to discover disease-modifying therapies. Here we show that N-acylethanolamine acid amidase (NAAA) is a critical control point in the progression to pain chronicity, which can be effectively targeted by small-molecule therapeutics that inhibit this enzyme. NAAA catalyzes the deactivating hydrolysis of palmitoylethanolamide, a lipid-derived agonist of the transcriptional regulator of cellular metabolism, peroxisome proliferator-activated receptor-α (PPAR-α). Our results show that disabling NAAA in spinal cord during a 72-h time window following peripheral tissue injury halts chronic pain development in male and female mice by triggering a PPAR-α-dependent reprogramming of local core metabolism from aerobic glycolysis, which is transiently enhanced after end-organ damage, to mitochondrial respiration. The results identify NAAA as a crucial control node in the transition to chronic pain and a molecular target for disease-modifying medicines.","journal":"Science Advances","year":2021,"id":159512,"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":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":422201,"name":"Kwang‐Mook Jung","orcid":"0000-0003-4096-6953","position":1,"is_corresponding":false},{"id":397673,"name":"Francesca Palese","orcid":"0000-0002-8426-8228","position":2,"is_corresponding":false},{"id":338066,"name":"André Obenaus","orcid":null,"position":3,"is_corresponding":false},{"id":670617,"name":"Alex Mabou Tagne","orcid":"0000-0003-3986-8344","position":4,"is_corresponding":false},{"id":352766,"name":"Lin Lin","orcid":"0000-0003-4702-7190","position":5,"is_corresponding":false},{"id":670618,"name":"Tarif Ibne Rashid","orcid":"0000-0001-7174-3213","position":6,"is_corresponding":false},{"id":670619,"name":"Romario Pacheco","orcid":"0000-0002-6348-3789","position":7,"is_corresponding":false},{"id":460776,"name":"Amandine Jullienne","orcid":"0000-0001-9458-055X","position":8,"is_corresponding":false},{"id":670620,"name":"Jade Ramirez","orcid":"0000-0003-2454-3862","position":9,"is_corresponding":false},{"id":670621,"name":"Marco Mor","orcid":"0000-0003-0199-1849","position":10,"is_corresponding":false},{"id":670622,"name":"Gilberto Spadoni","orcid":"0000-0001-7253-6902","position":11,"is_corresponding":false},{"id":225539,"name":"Cholsoon Jang","orcid":"0000-0001-6651-4213","position":12,"is_corresponding":false},{"id":314029,"name":"Andrea G. Hohmann","orcid":"0000-0003-0941-6435","position":13,"is_corresponding":false},{"id":397675,"name":"Daniele Piomelli","orcid":"0000-0002-2983-774X","position":14,"is_corresponding":false},{"id":397672,"name":"Yannick Fotio","orcid":"0000-0001-5193-2009","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:44:39.550981Z","pmid":"34678057","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":[]}