{"doi":"10.1016/j.ynpai.2024.100174","title":"Targeting Nav1.7 and Nav1.8 with a PIKfyve inhibitor to reverse inflammatory and neuropathic pain","abstract":"• The lipid kinase PIKfyve generates phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P 2 ). • SGC-PIKFYVE-1, a potent and selective inhibitor of PIKfyve, has been used as a chemical probe for this kinase. • PIKfyve inhibition reportedly changes membrane dynamics and ion transport. • SGC-PIKFYVE-1 inhibited voltage-gated sodium currents in rat sensory neurons. • SGC-PIKFYVE-1 reversed spared nerve injury-induced mechanical and cold nociception. PIKfyve (1-phosphatidylinositol 3-phosphate 5-kinase), a lipid kinase, plays an important role in generating phosphatidylinositol (3,5)-bisphosphate (PI(3,5)P 2 ). SGC-PIKFYVE-1, a potent and selective inhibitor of PIKfyve, has been used as a chemical probe to explore pathways dependent on PIKfyve activity. Based on reported changes in membrane dynamics and ion transport in response to PIKfyve inhibition, we hypothesized that pharmacological inhibition of PIKfyve could modulate pain. Acute treatment with SGC-PIKFYVE-1 (10 µM) inhibited voltage-gated sodium currents through the inhibition of Na v 1.7 and Na v 1.8 channels, without affecting voltage-gated calcium or potassium currents in sensory neurons. Additionally, systemic administration of SGC-PIKFYVE-1 (30 mg/kg) alleviated mechanical and cold sensitivity induced by neuropathic or inflammatory pain in both male and female mice, without causing motor impairments. Although other functions of PIKfyve are well characterized, its role in inhibiting chronic pain has not been fully elucidated. Our study provides proof-of-concept for this alternative approach to pain management. Collectively, these results highlight the inhibitory effects of PIKfyve as a promising avenue for further exploration in chronic pain treatment.","journal":"Neurobiology of Pain","year":2024,"id":451055,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":964287,"name":"Santiago Loya‐López","orcid":"0000-0001-6207-8370","position":1,"is_corresponding":false},{"id":1009680,"name":"Sophia M. Min","orcid":"0000-0001-9840-2996","position":2,"is_corresponding":false},{"id":964288,"name":"Aida Calderón‐Rivera","orcid":"0000-0002-0129-2848","position":3,"is_corresponding":false},{"id":254848,"name":"Kimberly Gómez","orcid":"0000-0003-1867-5041","position":4,"is_corresponding":false},{"id":548666,"name":"Rajesh Khanna","orcid":"0000-0002-2331-1667","position":5,"is_corresponding":false},{"id":376426,"name":"Alison D. Axtman","orcid":"0000-0003-4779-9932","position":6,"is_corresponding":false},{"id":1040610,"name":"Erick J. Rodríguez‐Palma","orcid":"0000-0002-9940-363X","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:02:41.417944Z","pmid":"39720155","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":[]}