Potassium Channel Openers Exhibit Cross-tolerance with Morphine in Two Experimental Models of Pain

Objective: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. Methods: Swiss albino mice of either gender weighing between 25-30 g were used for the study The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. Results: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. Conclusions: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.