Voluntary and forced exercises prevent the development of tolerance to analgesic effects of morphine in rats

Document Type: Original Article


1 Department of Physiology, Islamic Azad University, Damghan Branch, Damghan, Iran

2 Laboratory of Animal Addiction Models Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

3 Islamic Azad University, Semnan Branch, Semnan, Iran


Objective(s):Morphine is widely used to treat chronic pain. However, its utility is hindered by the development of tolerance to its analgesic effects. Despite the renowned beneficial effects of physical exercise on cognitive functions and signs of morphine withdrawal in morphine-dependent rats, little is known about the roles of voluntary and forced exercises in tolerance to analgesic effect of morphine in rats.
Materials and Methods: In this study, rats were injected with 10 mg/kg of morphine, once daily, SC over a period of 8 days of either voluntary or treadmill exercise. Following these injections, the percent of maximum possible effect (%MPE) of morphine was measured on the 1st, 4th, and 8th days by hot plate test.
Results: Both voluntary and forced exercises significantly increased pain threshold compared to the sedentary group (P<0.05). Voluntary and forced exercises also significantly increased potency of morphine compared to sedentary morphine group (P<0.05). Thus, we concluded that voluntary and forced exercises blocked the development of tolerance during 8 daily simultaneously treatments. When exercising rats were returned to sedentary conditions, sensitivity to the analgesic effects of morphine increased significantly and persisted during sedentary period in the exercising rats. In other words, %MPE of the exercising morphine-group increased significantly compared to saline group (P<0.05).
Conclusion: Our results showed that voluntary and forced exercises may be possible methods for treating the development of tolerance to analgesic effect of morphine in rats.


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