Chronic oral administration of docosahexaenoic acid reduces pain-related behaviors and functional disability in arthritis induced by Complete Freund’s Adjuvant. Docosahexaenoic acid (DHA) or vehicle was orally administered (p.o.) from day 15 until day 25 after initial Complete Freund’s Adjuvant (CFA) injection. (A) Assessment of arthritic joint pain included flinching of the affected limb (spontaneous pain-related behavior), horizontal exploratory activity and vertical rearing (pain-related functional disability), which were measured at days 0, 11, 18 and 25 following initial CFA injection. The intraarticular (i.a.) CFA injections resulted in significantly increasing spontaneous flinching and significantly decreasing functional outcomes as time progressed. (B) Three doses of DHA significantly reduced the number of spontaneous flinches in a dose-dependent manner; however, the maximum effect on spontaneous flinching was observed at a dose of 30 mg/kg. (C) Horizontal exploratory activity increased significantly in mice that received CFA injections following DHA treatment at doses of 30 and 100 mg/kg. (D) Oral administration of DHA did not significantly increase the number of vertical rearings at the three doses evaluated. Each bar represents the mean ± SEM. *P < 0.05 vs i.a. CFA + p.o. vehicle compared to its respective time period by two-way repeated-measures analysis of variance followed by post hoc Bonferroni correction.