Enadoline, a selective kappa-opioid receptor agonist shows potent antihyperalgesic and antiallodynic actions in a rat model of surgical pain

Enadoline is a highly selective and potent kappa-opioid receptor agonist. T his report describes and compares the activities of enadoline and morphine in a rat model of postoperative pain. A 1 cm incision through the muscle an d skin of the plantar surface of the right hind paw induced thermal hyperal gesia as well as static and dynamic allodynia lasting at least days. Postop erative testing was carried out using the planter test for thermal hyperalg esia, von Frey hairs for static allodynia and light stroking with a cotton bud for dynamic allodynia. A single i.v. dose of enadoline 15 min before su rgery dose-dependently (1-100 mu g/kg) blocked the development of thermal h yperalgesia as well as static and dynamic allodynia for over 24 h with resp ective MEDs of less than or equal to 1, 10 and 10 mu g/kg. The administrati on of enadoline (100 mu g/kg, i.v.), I h after surgery, completely blocked the maintenance of the hyperalgesic and allodynic responses, but its durati on of action was much shorter (2 h) than when administered before surgery. Previous studies have shown that administration of morphine (1-6 mg/kg, s.c .) 0.5 h before surgery can prevent the development of thermal hyperalgesia with a MED of less than or equal to 1 mg/kg, but it has little effect on s tatic allodynia. In the present study similar administration of morphine (1 -3 mg/kg), unlike enadoline, had no effect on the development of dynamic al lodynia. Morphine dose-dependently (1-6 mg/kg, s.c.) potentiated isoflurane -induced sleeping time and respiratory depression in the rat. However, whil st enadoline also (1-1000 mu g/kg, i.v.) potentiated isoflurane-induced sle eping time, it did not cause respiratory depression. It is suggested that e nadoline may possess therapeutic potential as a pre-emptive antihyperalgesi c and antiallodynic agent. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.