URB597 attenuated spontaneous activity in C-fiber nociceptors in HbSS-BERK sickle mice. Data illustrate the mean (±SEM) percent change in spontaneous activity at 30, 60, 90 and 120 min after various treatments. Intraplantar administration of URB597, which inhibits the breakdown of anandaminde (AEA) by fatty acid amide hydrolase (FAAH), decreased spontaneous activity relative to vehicle treatment at 30, 60, 90, and 120 min post-injection, and this was blocked by the CB1 receptor antagonist AM281. Pre-treatment with the CB2 receptor antagonist, AM630, failed to block the effect of URB597 and these fibers showed significantly lower rates of spontaneous activity relative to vehicle at 30, 60, 90, and 120 min post-injection. *p<.05, **p≤.01, ***p<.001 indicates significant differences from the vehicle-treated group.