Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats.
OBJECTIVE
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).


CONCLUSIONS
Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.
Wang
Cheng-Haung
CH
Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Taiwan, China.
Lee
Tsung-Hsing
TH
Tsai
Yi-Jung
YJ
Liu
Jong-Kang
JK
Chen
Yann-Jang
YJ
Yang
Lin-Cheng
LC
Lu
Cheng-Yuang
CY
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004361:Drug Tolerance; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine
D000701:Analgesics, Opioid; D011687:Purines; D000077546:Roscovitine; D009020:Morphine; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases