{"doi":"10.1101/2023.10.20.562785","title":"Mu opioid receptors gate the locus coeruleus pain generator","abstract":"The locus coeruleus (LC) plays a paradoxical role in chronic pain. Although largely known as a potent source of endogenous analgesia, increasing evidence suggests injury can transform the LC into a chronic pain generator. We sought to clarify the role of this system in pain. Here, we show optogenetic inhibition of LC activity is acutely antinociceptive. Following long-term spared nerve injury, the same LC inhibition is analgesic - further supporting its pain generator function. To identify inhibitory substrates that may naturally serve this function, we turned to endogenous LC mu opioid receptors (LC-MOR). These receptors provide powerful LC inhibition and exogenous activation of LC-MOR is antinociceptive. We therefore hypothesized that endogenous LC-MOR-mediated inhibition is critical to how the LC modulates pain. Using cell type-selective conditional knockout and rescue of LC-MOR receptor signaling, we show these receptors bidirectionally regulate thermal and mechanical hyperalgesia - providing a functional gate on the LC pain generator.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":392683,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"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":1166251,"name":"Chao‐Cheng Kuo","orcid":"0000-0001-9332-2743","position":1,"is_corresponding":false},{"id":998810,"name":"Samantha S. Dunn","orcid":null,"position":2,"is_corresponding":false},{"id":486622,"name":"Jenny Kim","orcid":"0000-0003-1393-7815","position":3,"is_corresponding":false},{"id":998232,"name":"Léa J. Becker","orcid":"0000-0002-5995-6088","position":4,"is_corresponding":false},{"id":1166252,"name":"Gustavo Borges","orcid":"0000-0001-8967-7891","position":5,"is_corresponding":false},{"id":561271,"name":"Loc V. Thang","orcid":null,"position":6,"is_corresponding":false},{"id":443197,"name":"Kyle E. Parker","orcid":"0000-0002-5432-6079","position":7,"is_corresponding":false},{"id":486628,"name":"Jordan G. McCall","orcid":"0000-0001-8295-0664","position":8,"is_corresponding":false},{"id":560801,"name":"Makenzie R. Norris","orcid":"0000-0002-1674-7761","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T01:18:56.730121Z","pmid":"37961541","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":[]}