Objective: We aimed to clarify the possible contributions of TRP and voltagedependentK+ channels to the analgesic effects of diclofenac, ketoprofen, etodolac,and dipyrone using the nonselective TRP channel blocker ruthenium red and thevoltage-dependent K+ channel blocker (Kv7; KCNQ) XE 991, respectively.Methods: We assessed the changes in the antinociceptive effects of diclofenac (50mg/kg, i.p.), ketoprofen (50 mg/kg, i.p.), etodolac (70 mg/kg, i.p.), and dipyrone (500mg/kg, i.p.) using ruthenium red (3 mg/kg, i.p.) and XE 991 (1 mg/kg, i.p.) beforetreatment in the hot plate, tail immersion, and writhing tests in mice.Results: In the tail immersion test, ruthenium red administration resulted in asignificant reversal in the analgesic effects of dipyrone, etodolac, and ketoprofen. Inthe hot plate test, a significant reversal was observed in the analgesic effect of onlydipyrone. In the tail immersion test, the administration of XE 991 induced a significantreversal in the analgesic effects of dipyrone and etodolac and a relative reversal in theanalgesic effects of ketoprofen and diclofenac. In the hot plate test, XE 991 produceda significant reversal in the analgesic effect of only ketoprofen, whereas it caused arelative reversal in the analgesic effects of other tested nonsteroidal anti-inflammatorydrugs (NSAIDs). In the writhing test, no significant change was observed after eitherXE 991 or ruthenium red administration.Concusions: Modulation of TRP and K+ channels may be involved in the centralanalgesic effects of NSAIDs. The clarification of different action mechanisms ofNSAIDs will contribute to new therapeutic approaches and provide guidance for newdrug development studies.