R-flurbiprofen decreased sensitization of C-fiber nociceptors in HbSS-BERK mice. The 24 C-fibers included in this analysis had a mean CV of 0.61 ± 0.04 m/s. Intraplantar administration of R-flurbiprofen administration (30 mg/10 mL) (A) decreased the rate of spontaneous discharge in C-fiber nociceptors, (B) increased mechanical response thresholds, and (C) decreased responses to stimulation with a 149 mN von Frey monofilament. (A) F[4, 68] = 3.9, P < .001. *Different from vehicle at P < .05. #Different from time 0 (preinjection) at P < .05. (B) F[3, 57] = 2.8, P < .05. Different from vehicle at **P < .01, ***P < .005). (C) F[4, 52] = 13.1, P < .001. #Different from vehicle at **P < .005, ***P < .001. ###Different from time 0 (preinjection) at P < .001. Mechanical response thresholds (in millinewtons) were converted to percent change scores to enable parametric tests to be used for analysis of the drug effect. Data are mean ± SEM and were analyzed using 2-way ANOVA for repeated measures with the Bonferroni t test. Representative examples of responses of 2 C-fiber nociceptors before and after intraplantar administration of vehicle and R-flurbiprofen are shown in panels D-F. (D) Conduction latencies: multiple traces were overlapped to show consistency. The left arrow indicates the onset of the stimulus, and the right arrow indicates the action potential of the fiber of interest. (E) Spontaneous activity over a 45-second period for each condition. (F) Raw data demonstrating the response to a 149-mN stimulus over 5 seconds for each condition. Vertical bars indicate voltage scale in panels E-F: vehicle = 0.50 V; R-flurbiprofen = 0.25 V.