The Role of TRP and K+ Ion Channels in Analgesic Effect of NSAIDs

Abstract

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