TRPV1 antagonist reversibly improves mechanical hypersensitivity in HbSS mice. The TRPV1 antagonist A-425619 (100 μmol/kg IP) reversibly improved mechanical hypersensitivity in HbSS mice compared with vehicle control injection (10% DMSO, 34% 2-hydroxypropyl β-cyclodextrin; P < .0001, Friedman repeated measures test; ††P < .01 and †P < .05, posthoc Dunn test comparing HbSS baseline with HbSS treated with A-425619 at 30 and 60 minutes, respectively; posthoc Dunn test also showed P < .001 for 30 minutes vs 120 minutes and P < .01 for 60 vs 120 minutes within the HbSS group treated with A-425619; HbSS n = 14). There was no significant difference in mechanical hypersensitivity in HbSS mice treated with vehicle (Friedman test, n = 12 HbSS-Vehicle). HbSS mice treated with A-425619 mice exhibited significantly improved mechanical hypersensitivity compared with HbSS mice treated with vehicle mice at 30, 60, and 90 minutes (P < .001, P < .001, P < .01, respectively; Mann Whitney U test), but not at 120 minutes (P > .05). All data are shown as means ± SEM.