Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

  • Ahmet Sevki Taskiran Departments of Physiology, Cumhuriyet University School of Medicine, Sivas, Turkey
  • Ercan Ozdemir Departments of Physiology, Cumhuriyet University, School of Medicine, Sivas, Turkey
  • Gokhan Arslan Departments of Physiology, Cumhuriyet University, School of Medicine, Sivas, Turkey
  • Yasar Tastemur Departments of Anatomy, Cumhuriyet University, School of Medicine, Sivas, Turkey
  • Ahmet Kemal Filiz Departments of Physiology, Cumhuriyet University, School of Medicine, Sivas, Turkey
Keywords: Phosphodiesterase type 5 inhibitors, tadalafil, nociception, morphine analgesia, morphine tolerance

Abstract

Aim: Tadalafil is a potent, selective and reversible inhibitor of phosphodiesterase type 5 (PDE5) enzyme breakdowning cyclic guanosine monophosphate (cGMP). In this study, we aimed to investigate the effects of tadalafil on nociception, morphine analgesia and tolerance.

Methods: In this study, 54 Wistar Albino (230-250 g) male rats were used. First of all, four different doses (2, 4, 8, 16 mg/kg) were used to determine the optimum effective dose of tadalafil on nociception. Optimum activity was found at 8 mg/kg and animals were divided into six groups: Saline (S), 8mg/kg tadalafil, 5mg/kg morphine (M), M+ tadalafil, morphine tolerance (MT) and MT+ tadalafil. Saline was given to the control group, tadalafil intraperitoneally and morphine subcutaneously administered at the indicated doses. To develop tolerance to morphine, 10mg/kg morphine was injected daily in the morning and evening for five days and tolerance was evaluated with single dose of morphine on sixth days. The resulting analgesic effect was measured with hot plate and tail flick analgesia tests and recorded at 30th, 60th, 90th and 120th minutes.

Results: Tadalafil showed anti-nociceptive effect when given alone at different doses (p<0.05). However, tadalafil significantly decreased the analgesic effect of morphine (p<0.05). In addition, tadalafil significantly increased the tolerance to morphine (p<0.05).

Conclusions: The phosphodiesterase type 5 inhibitor tadalafil have anti-nociceptive properties and it decreases analgesic effect of morphine, in addition improves tolerance development. These effects probably may occur via NO/cGMP pathway.

 

Published
2018-05-07