NSAİİ’ ların Analjezik Etkilerinde TRP ve K+ İyon Kanallarının Rolü

Amaç: Seçici olmayan TRP kanal blokörü rutenyum kırmızısı ve voltaj bağımlı K+ kanal blokörü XE 991 varlığında diklofenak, ketoprofen, etodolak ve dipironun analjezik etkilerine TRP’nin ve voltaj bağımlı K+kanallarının olası katkılarının incelenmesi amaçlanmıştır. Yöntemler: Rutenyum kırmızısı (RR) (3 mg / kg, ip) ve XE 991 (1 mg / kg, ip) varlığında, diklofenak (50 mg / kg, ip), ketoprofen (50 mg / kg, ip), etodolak (70 mg / kg, ip) ve dipironun (500 mg / kg, ip) antinosiseptif etkilerindeki değişiklikler, farelerde sıcak plaka, kuyruk daldırma ve kıvranma testlerinde araştırıldı. Bulgular: Kuyruk daldırma testinde RR uygulaması sonucu sadece dipiron, etodolak ve ketoprofen’in analjezik etkisinde anlamlı bir geri dönüş sağlanmıştır. Sıcak plaka testinde ise sadece dipiron’un analjezik etkisinde belirgin bir geri dönüş görülmektedir. XE 991 uygulanması kuyruk daldırma testinde dipiron ve etodolak’ın etkisinde anlamlı bir geri dönüş sağlarken, ketoprofen ve diklofenak’ın etkisinde göreceli bir geri dönüş sağlamaktadır. Sıcak plaka testinde ise sadece ketoprofen’in analjezik etkisinde anlamlı bir geri dönüş sağlarken, test edilen diğer non-steroidal antiinflamtuvar ilaçların (NSAİİ) etkisinde göreceli bir geri dönüş sağlamaktadır. Writhing testinde ise ne RR uygulamasında ne de XE 991 uygulaması sonucunda önemli bir değişiklik olmamıştır. Sonuç: Çalışmamızdan elde edilen sonuçlara göre NSAİİ’ın santral analjezik etkisinde TRP ve potasyum kanal modülasyonunun katkısının olabileceği düşünülmektedir. Bu projede kullanılan ve klinikte ağrı üzerine etkileri bilinen farmakolojik ajanların farklı etki mekanizmalarının aydınlatılmış olması, terapötik yaklaşımlara katkı sağlamakla birlikte yeni ilaç geliştirme çalışmalarında da yol gösterici olacağı düşünülmektedir.

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

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 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.

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