Effects of Dexamethasone, Clonidine, Tramadol and Nalbuphine on Fentanyl-Induced Hyperalgesia in Rats

Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to describe the effects of dexamethasone, clonidine, tramadol and nalbuphine on fentanyl-induced hyperalgesia in rats. After obtaining approval from the Committee for the Ethical Use of Animals (CEUA), 36 male Wistar rats were divided into 6 groups: Group 1 (GCSSL) wherein the rats received 1 ml 0.9% saline solution in two injections;Group 2 (GFTSL), received fentanyl at a dose of 100 ug·kg-1 followed by 1 ml 0.9% saline solution via intraperitoneal;the remaining groups (3, 4, 5, 6) received fentanyl at a dose of 100 ug·kg-1 following doses via intraperitoneal: Group 3 (GFTDX), dexamethasone at a dose of 1.0 mg·kg-1;Group 4 (GFTCL), clonidine at a dose of 20 mg·kg-1;Group 5 (GFTTR), tramadol at a dose of 50 mg·kg-1, and Group 6 (GFTNB), nalbuphine at a dose of 5 mg·kg-1. Under general anestesia using isoflurane, the animals were submitted to a surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments at 2 hours after the incision and on the 1st, 3rd and 5th days afterward. At 2 hours after the surgical procedure, there was lower intensity of pain in the fentanyl group (GFTSL) compared to the other groups, and on the fifth day there were no significant differences for pain intensity between groups. The results suggest the presence of fentanyl-induced hyperalgesia and efficacy in its reduction by dexamethasone, clonidine, tramadol and nalbuphine.

Effects of Ketoprofen, Ketamine, Lidocaine and Propofol on Fentanyl-Induced Hyperalgesia in Rats

Opioid-induced hyperalgesia negatively affects physiological pain management and presents a complex causal mechanism, involving, pharmacodynamic and pharmacokinetic factors of interactions with receptors, opioid-independent ascending systems and with pro-nociceptive systems. After approval by the CEUA, 42 male Wistar rats were divided into 7 groups: In group 1 (GCSSL) the animals received 1 ml of 0.9% saline solution intraperitoneally (IP);in group 2 (GFTSL), they received fentanyl at a dose of 100 ug·kg-1 IP;in the remaining groups (3, 4, 5, 6 and 7) the animals received IP, fentanyl at a dose of 100 ug·kg-1 followed also by IP route of: group 3 (GFTKP) ketoprofen at a dose of 5 mg·kg-1;group 4 GFTKT), ketamine up to a dose of 10.0 mg·kg-1;group 5 (GFTLI), incisional lidocaine up to a dose of 10 mg·kg-1;group 6 (GFTLP), intraperitoneal lidocaine up to a dose of 10 mg·kg-1 and group 7 (GFTPP), propofol up to a dose of 60 mg·kg-1. Under general anesthesia, all animals with a plantar surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments on the 2nd, 1st, 3rd and 5th days after treatment. In the 2nd hour and on the 5th day after the procedure, there was no hyperalgesia associated with the use of fentanyl, however, on the 1st and 3rd postoperative days there was hyperalgesia that was attenuated by ketoprofen, ketamine, lidocaine infiltrated in the incision and intraperitoneally, an effect not observed with the use of propofol. The results suggest fentanyl-induced hyperalgesia and the efficacy of ketoprofen, ketamine, incisional lidocaine and intraperitoneal lidocaine in reducing this effect.