The antinociceptive properties of Casearia sylvestris Sw. (Flacourtiaceae) were investigated in various models of pain-related behavior in mice. The hydroalcoholic crude extract of the plant (30-300mg/kg, per os) clearly inhibited nocifensive responses induced by ovalbumin (hindpaw licking) or acetic acid (writhes) in graded fashion. At 300mg/kg, the extract reduced nocifensive behaviors (from 71.1+/-13.3 to 14.8+/-9.3s; from 31.3+/-4.5 to 3.3+/-1.2 writhes, respectively) to similar extents as indomethacin (5mg/kg; 5.7+/-1.1s and 3.3+/-1.2 writhes, respectively). Significant antinociceptive effects in the hot plate test were only detected following administration of the highest extract dose, but this analgesic action appeared to be specific as the extract failed to change motor and exploratory activities. The antinociceptive effect of Casearia sylvestris extract in the acetic acid test was prevented by prior treatment with the non-selective opioid receptor antagonist naloxone (1mg/kg; 5.8+/-4.2 and 31.5+/-3.1 writhes in vehicle-treated and naloxone-treated groups, respectively), indicating that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, our investigation suggests a potential therapeutic benefit of Casearia sylvestris Sw. in treating conditions associated with inflammatory pain.