Clinical and Experimental Health Sciences

Abstract

Objective: We aimed to clarify the possible contributions of TRP and voltagedependent

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.