Coadministration of Novel Analgesic Isovaline with Tramadol Reduces Inflammatory Pain Response in Rats

Year 2024, , 52 - 58, 30.06.2024

Gözen Öksüz , Tufan Mert , Selma Yaman , Mahmut Arslan , Metin Kılınç , Nurten Seringeç Akkeçeci

https://doi.org/10.36516/jocass.1232464

Abstract

Aim: Isovaline is a new and promising analgesic with an antinociceptive effect and, unlike µ-opioid agonists, interacts with aminobutyric acid receptors without causing sedation or respiratory depression. In this study, we compare the effect on thermal hyperalgesia and mechanical allodynia coadministration of subcutaneous isovaline and tramadol with individual administrations in a carrageenan-induced hind paw inflammatory pain model in rats.
Methods: In this study, isovaline, tramadol, and the combination of isovaline and tramadol were subcutaneously administered to rats with carrageenan-induced inflammation of the hind paws. Hyperalgesia in response to thermal stimuli and allodynia in response to mechanic stimuli were assessed by using a thermal plantar test and a dynamic plantar aesthesiometer, respectively.
Results: The administration of subcutaneous isovaline 400mg/kg and tramadol 4mg/ kg combination effect was higher than the other groups on latencies and thresholds (P<0.01). Additionally, isovaline 400 mg/kg administration caused a statistical difference in latencies when compared with carrageenan, isovaline 2mg/kg, and tramadol 2mg/kg groups (P <0.005) and a statistical difference in thresholds when compared with carrageenan, tramadol 2mg/kg and tramadol 4 mg/kg groups (P <0.01). When isovaline 200 mg was used in combination with tramadol 2mg/kg, the latencies and thresholds were significantly higher than either treatment alone tramadol 2mg/kg and carrageenan groups (P≤ 0.001).
Conclusions: The results of this study demonstrated that the subcutaneous administration of isovaline had analgesic efficacy and was effective in combination with tramadol when used for the treatment of inflammatory pain.

Keywords

Inflammatory pain, isovaline, tramadol, paw edema

Supporting Institution

Kahramanmaras Sutcu Imam University Research Foundation

Project Number

2016/5-74M

Thanks

We thanks to Ph.D. Deniz Özel Erkan for statistical analysis.

Yeni Analjezik İzovalinin Tramadol ile Birlikte Uygulanması Sıçanlarda İnflamatuar Ağrı Cevabını Azaltır

Abstract

Amaç: İzovalin, antinosiseptif etkiye sahip yeni ve ümit verici bir analjeziktir ve µ-opioid agonistlerinin aksine, sedasyona veya solunum depresyonuna neden olmadan aminobütirik asit reseptörleri ile etkileşime girer. Bu çalışmada, sıçanlarda karragenan ile indüklenen arka pençe inflamatuar ağrı modelinde subkutan izovalin ve tramadolün termal hiperaljezi ve mekanik allodinia üzerindeki etkisini tek tek uygulamalarla karşılaştırıyoruz.
Yöntem: Bu çalışmada, izovalin, tramadol ve izovalin ve tramadol kombinasyonu, arka ayaklarında karragenan kaynaklı inflamasyon olan sıçanlara deri altından uygulandı. Termal uyaranlara yanıt olarak hiperaljezi ve mekanik uyaranlara yanıt olarak allodini, sırasıyla termal plantar testi ve dinamik plantar esteziyometre kullanılarak değerlendirildi.
Bulgular: Subkutan izovalin 400mg/kg ve tramadol 4mg/kg kombinasyon etkisi latans ve eşikler üzerine diğer gruplara göre daha yüksekti (P<0,001). Ayrıca, izovalin 400 mg/kg uygulaması, karragenan, izovalin 2mg/kg ve tramadol 2mg/kg grupları ile karşılaştırıldığında latanslarda istatistiksel farka (P <0,005) ve karragenan, tramadol 2mg/kg ve tramadol 4 mg/kg grupları ile karşılaştırıldığında eşiklerde istatistiksel farka neden olmuştur. (P <0,001). İzovalin 200 mg, tramadol 2mg/kg ile kombinasyon halinde kullanıldığında, latans ve eşikler, tek başına tramadol 2mg/kg ve karragenan gruplarına göre önemli ölçüde daha yüksek olmuştur (P≤ 0.001).
Sonuç: Bu çalışmanın sonuçları, izovalinin subkutan uygulamasının analjezik etkinliğe sahip olduğunu ve inflamatuar ağrının tedavisi için kullanıldığında tramadol ile kombinasyon halinde etkili olduğunu göstermiştir.

Keywords

İnflamatuar ağrı, izovalin, tramadol, pençe ödemi

Project Number

2016/5-74M

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