{"doi":"10.3389/fncel.2022.853035","title":"Cisplatin Neurotoxicity Targets Specific Subpopulations and K+ Channels in Tyrosine-Hydroxylase Positive Dorsal Root Ganglia Neurons","abstract":"Among the features of cisplatin chemotherapy-induced peripheral neuropathy are chronic pain and innocuous mechanical hypersensitivity. The complete etiology of the latter remains unknown. Here, we show that cisplatin targets a heterogeneous population of tyrosine hydroxylase-positive (TH + ) primary afferent dorsal root ganglion neurons (DRGNs) in mice, determined using single-cell transcriptome and electrophysiological analyses. TH + DRGNs regulate innocuous mechanical sensation through C-low threshold mechanoreceptors. A differential assessment of wild-type and vitamin E deficient TH + DRGNs revealed heterogeneity and specific functional phenotypes. The TH + DRGNs comprise; fast-adapting eliciting one action potential (AP; 1-AP), moderately-adapting (≥2-APs), in responses to square-pulse current injection, and spontaneously active (SA). Cisplatin increased the input resistance and AP frequency but reduced the temporal coding feature of 1-AP and ≥2-APs neurons. By contrast, cisplatin has no measurable effect on the SA neurons. Vitamin E reduced the cisplatin-mediated increased excitability but did not improve the TH + neuron temporal coding properties. Cisplatin mediates its effect by targeting outward K + current, likely carried through K2P18.1 (Kcnk18 ), discovered through the differential transcriptome studies and heterologous expression. Studies show a potential new cellular target for chemotherapy-induced peripheral neuropathy and implicate the possible neuroprotective effects of vitamin E in cisplatin chemotherapy.","journal":"Frontiers in Cellular Neuroscience","year":2022,"id":282204,"datarank":0.4359925538256563,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.10640886722522334,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.10640886722522334,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":8,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707870,"name":"Yingying Chen","orcid":"0000-0001-5890-5302","position":1,"is_corresponding":false},{"id":377837,"name":"Seojin Park","orcid":null,"position":2,"is_corresponding":false},{"id":400688,"name":"Jeong Han Lee","orcid":"0000-0002-4616-0355","position":3,"is_corresponding":false},{"id":475490,"name":"Maria C. Perez-Flores","orcid":"0000-0002-2166-5648","position":4,"is_corresponding":false},{"id":958256,"name":"Jinsil Choi","orcid":null,"position":5,"is_corresponding":false},{"id":376797,"name":"Ebenezer N. Yamoah","orcid":"0000-0002-9797-085X","position":6,"is_corresponding":false},{"id":381726,"name":"Carrie J. Finno","orcid":"0000-0001-5924-0234","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:15.734856Z","pmid":"35586548","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":[]}