{"doi":"10.1016/j.celrep.2023.113316","title":"Pain and itch coding mechanisms of polymodal sensory neurons","abstract":"Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD + neurons represent a major polymodal population and mediate both mechanical pain and nonhistaminergic itch. Here, we show that chemogenetic activation of MrgprD + neurons elicited both pain- and itch-related behavior in a dose-dependent manner, revealing an unanticipated compatibility between pain and itch in polymodal neurons. While VGlut2-dependent glutamate release is required for both pain and itch transmission from MrgprD + neurons, the neuropeptide neuromedin B (NMB) is selectively required for itch signaling. Electrophysiological recordings further demonstrated that glutamate synergizes with NMB to excite NMB-sensitive postsynaptic neurons. Ablation of these spinal neurons selectively abolished itch signals from MrgprD + neurons, without affecting pain signals, suggesting a dedicated itch-processing central circuit. These findings reveal distinct neurotransmitters and neural circuit requirements for pain and itch signaling from MrgprD + polymodal sensory neurons, providing new insights on coding and processing of pain and itch.","journal":"Cell Reports","year":2023,"id":325964,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":644265,"name":"Haowu Jiang","orcid":"0000-0003-2477-5970","position":1,"is_corresponding":false},{"id":1044834,"name":"Cheng-Chiu Huang","orcid":null,"position":2,"is_corresponding":false},{"id":620854,"name":"Fengxian Li","orcid":"0000-0002-3307-1468","position":3,"is_corresponding":false},{"id":873923,"name":"William Olson","orcid":"0000-0001-9893-9726","position":4,"is_corresponding":false},{"id":644266,"name":"Weishan Yang","orcid":"0000-0001-7735-3128","position":5,"is_corresponding":false},{"id":1044835,"name":"Michael S. Fleming","orcid":null,"position":6,"is_corresponding":false},{"id":452120,"name":"Guang Yu","orcid":null,"position":7,"is_corresponding":false},{"id":1044836,"name":"George E. Hoekel","orcid":null,"position":8,"is_corresponding":false},{"id":636195,"name":"Wenqin Luo","orcid":"0000-0002-2486-807X","position":9,"is_corresponding":false},{"id":644269,"name":"Qin Liu","orcid":"0000-0002-1589-0881","position":10,"is_corresponding":false},{"id":634227,"name":"Changxiong Guo","orcid":"0000-0002-2886-8536","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"37889748","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":[]}