DİDEM DAL, M. Alper SALMAN, A. Ebru SALMAN, Alper B. İSKİT, Ülkü AYPAR

Kimyasal ağrı modelinde farklı tramadol dozlarının ve nitrik oksit sentaz inhibitörlerinin etkileşimi

Tramadol, opioid, serotonerjik ve noradrenerjik etki mekanizmaları olan santral etkili bir sentetik analjeziktir. Bu çalışmada nitrik oksit sentaz (NOS) inhibitörleri L-NAME ve 7 Nitro indazol (7NI)'ün tramadol ile kimyasal bir ağrı modelinde etkileşimlerini incelemeyi amaçladık. Yetmişiki erişkin dişi Swiss Webster faresi randomize olarak ön tedaviye göre 3 ana gruba ayrıldı ve intraperitoneal (i.p.) olarak serum fizyolojik (Grup 1=24), L-NAME (Grup 11=24) 10 mg $kg^-1$ ve 7-NI (Grup 111=24) 3 mg $kg^-1$ uygulandı. Her bir ana grup 4 alt gruba ayrılarak 12 alt grup (n=6) oluşturuldu. Üç ana grubun alt gruplarına ön tedavi uygulanmasından 20 dk sonra serum fizyolojik, tramadol 10 mg $kg^-1$ , 20 mg $kg^-1$ ve 40 mg $kg^-1$ uygulandı. Tüm gruplardaki farelere serum fizyolojik veya Tramadol uygulanmasından 20 dk. sonra %3 asetik asit 300 mg $kg^-1$ i.p. verildi. Enjeksiyonlardan 5 dakika sonra 15 dakika süre ile farelerin kıvranma sayılan değerlendirildi. Serum fizyolojik, L-NAME ve 7-NI ön tedavisi aldıktan sonra üç grupta kıvranma sayıları açısından gruplar karşılaştırıldığında istatistiksel olarak anlamlı bir fark gözlenmedi. 7NI ön tedavisi alan grupta 10, 20 ve 40 mg $kg^-1$ tramadol alt gruplarında kıvranma sayıları arasında fark bulunmazken, SF alt grubuna göre anlamlı azalma vardı (p

Anahtar Kelimeler:

Tramadol, Nitrik oksit, Enzim inhibitörleri, Nitrik-oksit sentaz, Sıçan, Sprague-Dawley

The interaction of nitric oxide synthase inhibitors and different doses of tramadol in the chemical pain model

Tramadol is a centrally acting synthetic analgesic with opioid, serotonergic and noradrenergic mechanisms of action. We aimed to investigate the interaction of nitric oxide synthase (NOS) inhibitors L-NAME and 7 Nitro indazole (7NI) mth tramadol by using a chemicalpain model. Seventy two adultfemale Swiss Webster mice were randomly allocated into 3 groups to receive either intraperitoneal saline, L-NAME 10 mg $kg^-1$ or 7-NI 3 mg $kg^-1$. Each main group was divided into 4 subgroups to make 12 groups. 20 minutes after the first injection, another intraperitoneal injection of saline, Tramadol 10 mg $kg^-1$, Tramadol 20 mg $kg^-1$ or Tramadol 40 mg $kg^-1$ were applied to the subgroups of these three main groups. The mice in ali groups received 3% acetic acid 300 mg $kg^-1$ i.p. another 20 minutes after the second injections. Writhing of mice were observed following 5 minutes after injections, for the subsequent 15 minutes. No statistically significant differences were observed with the three doses of Tramadol or saline when the pretreatments with saline, L-NAME or 7-NI were compared. in 7-NI pretreated group, 10, 20, 40 mg $kg^-1$ Tramadol subgroups were similar, with the exception of şaline subgroup (p<0.05). Tramadol 20 and 40 mg $kg^-1$ subgroups of Şaline and L-NAME groups, a significant decrease vcasfound in writhing numbers when compared to şaline and Tramadol 10 mg $kg^-1$ subgroups (p<0.05). We concluded that 20 mg $kg^-1$ tramadol injection provided enough analgesic effect and the nitric oxide synthase inhibitors L-NAME or 7NI did not significantly influence the analgesic effect of tramadol in the chemicalpain model we used.

Keywords:

Tramadol, Nitric Oxide, Enzyme Inhibitors, Nitric-Oxide Synthase, Rats, Sprague-Dawley,

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