{"doi":"10.1007/s12035-020-02276-8","title":"Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain","abstract":"Sigma-1 receptors (Sig-1Rs) are endoplasmic reticulum (ER) chaperones implicated in neuropathic pain. Here we examine if the Sig-1R may relate to neuropathic pain at the level of dorsal root ganglia (DRG). We focus on the neuronal excitability of DRG in a \"spare nerve injury\" (SNI) model of neuropathic pain in rats and find that Sig-1Rs likely contribute to the genesis of DRG neuronal excitability by decreasing the protein level of voltage-gated Cav2.2 as a translational inhibitor of mRNA. Specifically, during SNI, Sig-1Rs translocate from ER to the nuclear envelope via a trafficking protein Sec61β. At the nucleus, the Sig-1R interacts with cFos and binds to the promoter of 4E-BP1, leading to an upregulation of 4E-BP1 that binds and prevents eIF4E from initiating the mRNA translation for Cav2.2. Interestingly, in Sig-1R knockout HEK cells, Cav2.2 is upregulated. In accordance with those findings, we find that intra-DRG injection of Sig-1R agonist (+)pentazocine increases frequency of action potentials via regulation of voltage-gated Ca2+ channels. Conversely, intra-DRG injection of Sig-1R antagonist BD1047 attenuates neuropathic pain. Hence, we discover that the Sig-1R chaperone causes neuropathic pain indirectly as a translational inhibitor.","journal":"Molecular Neurobiology","year":2021,"id":180954,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":460104,"name":"Nino Goguadze","orcid":null,"position":1,"is_corresponding":false},{"id":460106,"name":"Yuriko Kimura","orcid":null,"position":2,"is_corresponding":false},{"id":460105,"name":"Yuko Yasui","orcid":null,"position":3,"is_corresponding":false},{"id":679841,"name":"Bin Pan","orcid":"0000-0002-5134-2508","position":4,"is_corresponding":false},{"id":714182,"name":"Tzu‐Yun Wang","orcid":"0000-0002-0561-9967","position":5,"is_corresponding":false},{"id":731117,"name":"Yoki Nakamura","orcid":"0000-0001-9226-676X","position":6,"is_corresponding":false},{"id":680252,"name":"Yu-Ting Lin","orcid":"0000-0002-1045-1871","position":7,"is_corresponding":false},{"id":679840,"name":"Quinn H. Hogan","orcid":"0000-0002-5445-5276","position":8,"is_corresponding":false},{"id":731118,"name":"Katherine L. Wilson","orcid":"0000-0003-1402-4735","position":9,"is_corresponding":false},{"id":458674,"name":"Tsung‐Ping Su","orcid":"0000-0003-2384-6925","position":10,"is_corresponding":false},{"id":467035,"name":"Hsiang-en Wu","orcid":"0000-0003-4492-2077","position":11,"is_corresponding":false},{"id":458672,"name":"Shao‐Ming Wang","orcid":"0000-0003-1479-9100","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-18T23:48:01.257885Z","pmid":"33459966","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":[]}