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Updated: Aug 23, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats
Cheng-Haung Wang1, Tsung-Hsing Lee, Yi-Jung Tsai
1Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Taiwan, China.
Aim:
To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats.
Methods:
Tail-flick test as pain threshold measurement and intrathecal injection techniques were used.
Results:
Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 microg/h for 5 d. Co-administration of intrathecal roscovitine 1 microg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose-response curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response).
Conclusion:
Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.
