SEROTONERJIK VE NORADRENERJIK MODÜLASYONUN ROSMARINIK ASIT ANALJEZISINE KATKISI

Abstract

Bu çalışmada, 0.3, 1 ve 3 mg/kg (p.o.) rosmarinik asitin farelerde santral analjezik etkinliğinin sıcak-plaka ve kuyruk-batırma testleri, periferal analjezik etkinliğinin ise asetik asit ile indüklenen kıvranma-testi ile değerlendirilmesi planlanmıştır. Ayrıca bu etkinliğe 5HT2A/2C reseptör antagonisti ketanserin (1 mg/kg, i.p.) kullanılarak serotonerjik ve α2-adrenerjik antagonisti yohimbin (1 mg/kg, i.p.) kullanılarak noradrenerjik modülasyonun katkısının araştırılması amaçlanmıştır. Sıcak-plaka testinde 1 mg/kg rosmarinik asit 45. dakikada, 3 mg/kg rosmarinik asit ise 30., 45. ve 60. dakikada, kuyruk-batırma testinde 1 ve 3 mg/kg rosmarinik asit 45 ve 60. dakikada termal uyarana karşı verilen cevabının süresini uzatmıştır. Kıvranma-testinde ise, 45. dakikada uygulanan rosmarinik asit tüm dozlarda kıvranma sayılarını anlamlı olarak azaltmıştır. Ketanserin, rosmarinik asitin oluşturduğu etkiyi sıcak-plaka ve kıvranma-testinde değiştirmemiş, kuyruk-batırma testinde ise anlamlı olarak geri çevirmiştir. Yohimbin, rosmarinik asitin oluşturduğu etkiyi sıcak-plaka testinde göreceli olarak, kuyruk-batırma ve kıvranma- testinde ise anlamlı olarak geri çevirmiştir. Rosmarinik asit hem inici inhibitör yolakta yer alan serotonerjik ve noradrenerjik sistemi değişik düzeylerde modüle ederek, hem de periferik noradrenerjik sistemi stimüle ederek santral ve periferal analjezik etki sağlamaktadır. Sonuç olarak, ağrının eşlik ettiği rahatsızlıklarda yardımcı ilaç olarak kullanılabilecek doğal bir ilaç adayıdır.

Keywords

• Rosmarinik asit, ağrı, serotonin, noradrenalin

The Participation of Serotonergic and Noradrenergic Modulation in Rosmarinic Acid-Induced Analgesia

Abstract

It was aimed to evaluate the central analgesic activity of 0.3, 1 and 3 mg/kg (p.o.) rosmarinic acid in mice by hot- plate and tail-immersion tests in a time dependent manner and the peripheral analgesic activity by acetic acid-induced writhing-test. Furthermore one of the other purpose of the study is to research the involvement of serotonergic and noradrenergic modulation on rosmarinic acid-induced analgesia by using 1 mg/kg (i.p.) ketanserin, 5HT2A/2C receptor antagonist, and yohimbine, α2-adrenoceptor antagonist, respectively. The enhanced withdrawal responses to thermal stimuli were observed 45 minutes after the administration of 1 mg/kg rosmarinic acid; 30, 45 and 60 minutes after the administration of 3 mg/kg rosmarinic acid in hot-plate test; 45 and 60 minutes after the administration of 1 and 3 mg/kg rosmarinic acid in tail-immersion test. In writhing-test, the number of writhing significantly decreased 45 minutes after the administration of 0.3, 1 and 3 mg/kg rosmarinic acid. Rosmarinic acid-induced antinociception was significantly reversed by ketanserin only in tail-immersion test while it was reversed significantly in both tail-immersion and writhing-test by yohimbine. Rosmarinic acid provides analgesic effects by modulating serotonergic and noradrenergic systems that are located in descending inhibitory pathway and by stimulating peripheral noradrenergic system. Therefore, rosmarinic acid is a natural agent that can be used safely as a co-adjuvant in pain management

Keywords

• Rosmarinic acid, pain, serotonin, noradrenalin

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