{"doi":"10.1016/j.ynpai.2024.100168","title":"Sodium channels Nav1.7, Nav1.8 and pain; two distinct mechanisms for Nav1.7 null analgesia","abstract":null,"journal":"Neurobiology of Pain","year":2024,"id":619358,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1598281,"name":"Alexandros H. Kanellopoulos","orcid":null,"position":1,"is_corresponding":false},{"id":1598282,"name":"Naxi Tian","orcid":null,"position":2,"is_corresponding":false},{"id":1107576,"name":"Jun Zhou","orcid":"0000-0003-4799-8165","position":3,"is_corresponding":false},{"id":1598283,"name":"Gozde Caan","orcid":null,"position":4,"is_corresponding":false},{"id":1598284,"name":"Riccardo Chiozzi","orcid":null,"position":5,"is_corresponding":false},{"id":394958,"name":"Konstantinos Thalassinos","orcid":"0000-0001-5072-8428","position":6,"is_corresponding":false},{"id":12586,"name":"Cankut Çubuk","orcid":"0000-0003-4646-0849","position":7,"is_corresponding":false},{"id":1392194,"name":"Myles J. Lewis","orcid":null,"position":8,"is_corresponding":false},{"id":1367922,"name":"James J. Cox","orcid":"0000-0002-9129-8011","position":9,"is_corresponding":false},{"id":349994,"name":"Jing Zhao","orcid":"0000-0001-9480-7638","position":10,"is_corresponding":false},{"id":1598287,"name":"Christopher G. Woods","orcid":null,"position":11,"is_corresponding":false},{"id":1198866,"name":"John N. Wood","orcid":"0000-0002-9166-8158","position":12,"is_corresponding":false},{"id":1598280,"name":"Federico Iseppon","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sodium channels Nav1.7, Nav1.8 and pain; two distinct mechanisms for Nav1.7 null analgesia","abstract":"• The 0.5% polydimethylsiloxane addition enhanced removal efficiency to 85% • Fungal biofilter had higher degradation ability compared to bacterial biofilter. • The biofilters evolved into a co-degradation system. • Sphingomonas and Sphingobium were the dominant bacterial species. • Fusarium and Cladosporium became the primary fungal components. Genetic deletion and pharmacological inhibition are distinct approaches to unravelling pain mechanisms, identifying targets and developing new analgesics. Both approaches have been applied to the voltage-gated sodium channels Na v 1.7 and Na v 1.8. Genetic deletion of Na v 1.8 in mice leads to a loss of pain and antagonists are effective analgesics. The situation with Nav1.7 is more complex. Complete embryonic loss of Na v 1.7 in humans or in mouse sensory neurons leads to anosmia as well as profound analgesia as a result of diminished neurotransmitter release. This is mediated by enhanced endogenous opioid signaling in humans and mice. In contrast, anosmia is opioid-independent. Sensory neuron excitability and autonomic function appear to be normal. Adult deletion of Na v 1.7 in sensory neurons also leads to analgesia, but through diminished sensory and autonomic neuron excitability. There is no opioid component of analgesia or anosmia as shown by a lack of effect of naloxone. Pharmacological inhibition of Na v 1.7 in mice and humans leads both to analgesia and dramatic side-effects on the autonomic nervous system with no therapeutic window. These data demonstrate that specific Na v 1.7 channel blockers will fail as analgesic drugs. The viability of embryonic null mutants suggests that there are compensatory changes to replace the lost Na v 1.7 channel. Here we show that sensory neuron sodium channels Na v 1.1, Na v 1.2 and β4 subunits detected by Mass Spectrometry are upregulated in Na v 1.7 embryonic null neurons and, together with other proteome changes, potentially compensate for the loss of Na v 1.7. Interestingly, many of the upregulated proteins are known to interact with Nav1.7.","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39559752","pmcid":"PMC11570969","openalex_id":"https://openalex.org/W4403329692","authors":[],"funders":[{"funder_name":"Cancer Research UK","grant_id":"185341","title":null},{"funder_name":"Versus Arthritis","grant_id":"21950","title":null},{"funder_name":"UK Research and Innovation Medical Research Council","grant_id":"MR/V012509/1","title":"MICA: Development and Validation of a Transcriptomic-Based Model for Classifying and Predicting Treatment Response in Rheumatoid Arthritis (TRACT-RA)"},{"funder_name":"UK Research and Innovation Medical Research Council","grant_id":"571476","title":null},{"funder_name":"Wellcome Trust","grant_id":"221521/Z/20/Z","title":null},{"funder_name":"Wellcome Trust","grant_id":"221521","title":"Expanding the proteomics and establishing top-down capabilities for the UCL Mass Spectrometry Science Technology Platform."},{"funder_name":"NIHR Cambridge Biomedical Research Centre","grant_id":"","title":null}],"total_grants":7,"fwci":1.9402,"citation_percentile":0.86633416,"influential_citations":0,"citation_trend":[{"year":2025,"count":7},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.ynpai.2024.100168","host_type":"journal"},{"url":"https://doi.org/10.1016/j.ynpai.2024.100168","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2452073X24000199?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2452073X24000199?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39559752","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11570969","host_type":"repository"},{"url":"https://qmro.qmul.ac.uk/xmlui/handle/123456789/104428","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11570969/pdf/main.pdf","host_type":"repository"},{"url":"https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/104428/2/Sodium%20channels%20Na%26lt%3bsub%26gt%3bv%26lt%3bsub%26gt%3b1.7%2c%20Na%26lt%3bsub%26gt%3bv%26lt%3bsub%26gt%3b1.8%20and%20pain%3b%20two%20distinct%20mechanisms%20for%20Na%26lt%3bsub%26g.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11570969","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11570969?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1016/j.ynpai.2024.100168","host_type":""},{"url":"https://www.repository.cam.ac.uk/handle/1810/382548","host_type":""}],"fields_of_study":["Ion channel regulation and function","Pain Mechanisms and Treatments","Anesthesia and Sedative Agents","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["NAV1","Nav1.5","Sodium channel","Medicine","Anesthesia","Chemistry","Sodium","Sodium channels","Drugs","Pain","Side effects","Nav1.7","Nav1.8","Genetic Deletion","Original Research Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"omim"},{"name":"pxd"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T06:52:57.990437Z","pmid":null,"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":[]}