Ozgen, BeyzaSenol, Sefika PinarYilmaz, Dilsah EzgiTemiz-Resitoglu, MeryemBahceli, OmerTunctan, Bahar2025-03-172025-03-1720230428-02962603-557Xhttps://doi.org/10.3897/pharmacia.70.e108995https://hdl.handle.net/20.500.13099/1540Objectives: This study aimed to investigate the effect of the gasdermin D (GSDMD) and mixed lineage kinase domain-like pseudokinase (MLKL) inhibitor, necrosulfonamide (NSA), on lipopolysaccharide (LPS)-induced hyperalgesia in mice. Methods: Reaction time to a thermal stimulus within 30 seconds was measured in male mice injected with saline, LPS, and/or NSA after 6 hours using the hot plate test. Immunoblotting studies were performed to determine changes in caspase-11/GSDMD-mediated pyroptosis, receptor-interacting serine/threonine-protein kinase (RIPK) 1/RIPK3/MLKL necrosome-mediated necroptosis, demyelination, and remyelination in the brains and spinal cords of animals. Results: NSA demonstrated significant antinociceptive activity compared with LPS-treated mice. In the tissues of LPS-treated mice, NSA decreased expression of caspase-11 p20, p30-GSDMD, interleukin-1 beta, high-mobility-group-box 1, and semaphorin 3A, and activity of RIPK1, RIPK3, and MLKL. NSA also increased the expression of myelin proteolipid protein. Conclusion: Therefore, NSA may have therapeutic potential in the treatment of inflammatory painful conditions due to bacterial infections.eninfo:eu-repo/semantics/openAccessInflammatory hyperalgesialipopolysaccharidenecroptosispyroptosisnecrosulfonamideArticle10.3897/pharmacia.70.e10899570413451354N/AWOS:0011634667000022-s2.0-85180784170Q2