Dexmedetomidine, an α2 agonist, increases the morphine analgesic effect and decreases morphine tolerance development by suppressing oxidative stress and TNF/IL-1 signalling pathway in rats Dexmedetomidina, un agonista de α2, incrementa el efecto analgésico de la morfina y reduce el desarrollo de tolerancia a la morfina suprimiendo el estrés oxidativo y la vía de señalización de TNF/IL-1 en ratas


Avcı O., Taşkıran A. Ş., Gündoğdu O.

Revista Espanola de Anestesiologia y Reanimacion, cilt.70, sa.6, ss.327-340, 2023 (ESCI) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 70 Sayı: 6
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.redar.2022.04.003
  • Dergi Adı: Revista Espanola de Anestesiologia y Reanimacion
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, EMBASE, MEDLINE, DIALNET
  • Sayfa Sayıları: ss.327-340
  • Anahtar Kelimeler: Caspase-3, Caspase-9, Dexmedetomidine, Morphine analgesia, Morphine tolerance, Oxidative stress, TNF/IL-1
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

Background: The aim of the present study is to examine the possible effect de dexmedetomidine on the development of morphine tolerance in rats including nociception, morphine analgesia, apoptosis, oxidative stress, and tumour necrosis factor (TNF)/ interleukin-1 (IL-1) pathways. Materials and methods: In this study, 36 Wistar Albino (225–245 g) rats were used. Animals were divided into 6 groups: saline (S), 20 mcg/kg dexmedetomidine (D), 5 mg/kg morphine (M), M + D, morphine tolerance (MT), and MT + D. The analgesic effect was measured with hot plate and tail-flick analgesia tests. After the analgesia tests, the dorsal root ganglia (DRG) tissues were excised. Oxidative stress parameters [total antioxidant status (TAS), total oxidant status (TOS)], TNF, IL-1 and apoptosis enzymes (Caspase-3, Caspase-9), were measured in DRG tissues. Results: Dexmedetomidine showed an antinociceptive effect when given alone (p < 0.05 to p < 0.001). In addition, dexmedetomidine increased the analgesic effect of morphine (p < 0.001), and also decreased the tolerance to morphine at a significant level (p < 0.01 to p < 0.001). Moreover, it decreased oxidative stress (p < 0.001) and TNF/IL-1 levels when given as an additional drug of single-dose morphine and morphine tolerance group (p < 0.001). Furthermore, dexmedetomidine decreased Caspase-3 and Caspase-9 levels after tolerance development (p < 0.001). Conclusión: Dexmedetomidine has antinociceptive properties, and it increases the analgesic effect of morphine and also prevents tolerance development. These effects probably occur by the modulation of oxidative stress, inflammation and apoptosis.