{"doi":"10.1101/2023.06.08.544200","title":"Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain","abstract":"Chronic pain often alternates between transient remission and relapse of severe pain. While most research on chronic pain has focused on mechanisms maintaining pain, there is a critical unmet need to understand what prevents pain from re-emerging in those who recover from acute pain. We found that interleukin (IL)-10, a pain resolving cytokine, is persistently produced by resident macrophages in the spinal meninges during remission from pain. IL-10 upregulated expression and analgesic activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of IL-10 signaling or δOR triggered relapse to pain in both sexes. These data challenge the widespread assumption that remission of pain is simply a return to the naïve state before pain was induced. Instead, our findings strongly suggest a novel concept that: remission is a state of lasting pain vulnerability that results from a long-lasting neuroimmune interactions in the nociceptive system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396652,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":909095,"name":"Jaewon Sim","orcid":"0009-0007-4560-3525","position":1,"is_corresponding":false},{"id":1172085,"name":"Kimberly B. Clark","orcid":"0000-0002-9368-2404","position":2,"is_corresponding":false},{"id":1172421,"name":"Geron Matan","orcid":null,"position":3,"is_corresponding":false},{"id":1041189,"name":"Karli Monahan","orcid":null,"position":4,"is_corresponding":false},{"id":1172086,"name":"C. J. Evans","orcid":"0000-0001-6830-9205","position":5,"is_corresponding":false},{"id":1172422,"name":"Po Beng","orcid":null,"position":6,"is_corresponding":false},{"id":1172423,"name":"Jiacheng “Vicky”","orcid":null,"position":7,"is_corresponding":false},{"id":252466,"name":"Cobi J. Heijnen","orcid":"0000-0002-1928-3050","position":8,"is_corresponding":false},{"id":261858,"name":"Robert Dantzer","orcid":"0000-0001-9399-6107","position":9,"is_corresponding":false},{"id":267492,"name":"Grégory Scherrer","orcid":"0000-0002-1983-5126","position":10,"is_corresponding":false},{"id":334498,"name":"Annemieke Kavelaars","orcid":"0000-0001-5162-0419","position":11,"is_corresponding":false},{"id":856377,"name":"Matthew Bernard","orcid":"0000-0002-1891-6880","position":12,"is_corresponding":false},{"id":740084,"name":"Yasser A. Aldhamen","orcid":"0000-0002-9560-8013","position":13,"is_corresponding":false},{"id":377211,"name":"Joseph K. Folger","orcid":"0000-0001-9928-3853","position":14,"is_corresponding":false},{"id":335093,"name":"Geoffroy Laumet","orcid":"0000-0001-6752-3592","position":15,"is_corresponding":false},{"id":997061,"name":"Kufreobong E. Inyang","orcid":"0000-0002-0735-6945","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:19:31.472087Z","pmid":"37333074","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":[]}