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Several antidepressants have been used to treat severe pain in clinics. Recently, it has been shown that ellagic acid (EA), a major constituent of pomegranate juice, produced antinociceptive and anti-inflammatory effect through the central and peripheral sites of action.

In this study, we examined the interaction between EA and venlafaxine (VLF) on pain induced by intraperitoneal acetic acid in mice using isobolographic analysis.

EA (0.3–10 mg/kg, ip) and VLF (3–60 mg/kg, ip) produced a dose-dependent inhibition of the writhing response evoked by acetic acid. Fifty percent effective dose (ED₅₀) values against writhing behaviors were 1.02 (0.86–1.19) mg/kg and 12.37 (9.74–15.37) mg/kg for EA and VLF, respectively, and also with higher potency than that of VLF. Co-administration of increasing fractional increments of ED₅₀ doses of EA and VLF produced synergistic …