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Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.<\/jats:p>","DOI":"10.1101\/2025.01.23.633455","type":"posted-content","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:30:11Z","timestamp":1737765011000},"source":"Crossref","is-referenced-by-count":1,"title":["Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0168-657X","authenticated-orcid":false,"given":"Xiangfei","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veselina","family":"Petrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingya","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean Shuailin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jeong","family":"Yong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoung Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-9338","authenticated-orcid":false,"given":"Omer","family":"Barkai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakanksha","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-2101","authenticated-orcid":false,"given":"William","family":"Renthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Lirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J.","family":"Woolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025012804001179000_2025.01.23.633455v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2019.01.003"},{"key":"2025012804001179000_2025.01.23.633455v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anclin.2022.04.002"},{"key":"2025012804001179000_2025.01.23.633455v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011279.pub3"},{"key":"2025012804001179000_2025.01.23.633455v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101786"},{"key":"2025012804001179000_2025.01.23.633455v1.5","doi-asserted-by":"crossref","unstructured":"Orlando, B. , Egeo, G. , Aurilia, C. , Fiorentini, G. & Barbanti, P. 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