A new pharmacological role for thalidomide: Attenuation of morphine-induced tolerance in rats

Objective

Tolerance to the analgesic effect is the main side effect of chronic administration of opioids. Several drugs have been studied to try to find agents to prevent the development of this phenomenon. In the present study we aimed to evaluate the effect of thalidomide on morphine-induced tolerance to the analgesic effect.

Methods

Groups of male rats were randomly rendered and received daily morphine in combination with thalidomide vehicle or thalidomide (2.5 mg/kg, 5 mg/kg, or 10 mg/kg, intraperitoneally). Nociception was measured using the plantar test apparatus. Latency time was recorded when the animal reacted to the light stimulus; licking or raising its hind paw. Treatments and evaluations continued until completion of tolerance to the analgesic effect of morphine.

Results

Our findings indicated that tolerance was achieved following 11 days of morphine administration, while thalidomide postponed the day of tolerance completion for 4 days (2.5 mg/kg and 5 mg/kg thalidomide) or 10 days (10 mg/kg thalidomide). Moreover, thalidomide prevented the morphine-induced shift to the right of the ED₅₀ in the dose–response curve.

Conclusion

It was concluded that thalidomide attenuated the morphine-induced tolerance to the analgesic effect.