Abstract
Aim:
To investigate effects of the cyclin-dependent kinase5 (Cdk5) inhibitor roscovitine on formalin-induced nociceptive responses in rats.
Methods:
The flinch response as a methood of pain threshold measurement and intrathecal injection techniques were used. Cdk5 and phosphorylation of its downstream target, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa), were investigated by Western blot analysis.
Results:
Rats demonstrated a typical flinch response after formalin injection. Intrathecal roscovitine injections significantly suppressed the flinch response in a dose-dependent manner. Western blot analysis showed that phosphorylated DARPP-32 at Thr75 increased in concentration after formalin hyperalgesia, with this effect reduced by roscovitine administration. This antinociception was partially attenuated by administration of naloxone before the formalin test.
Conclusion:
DARPP-32 phosphorylation is involved in acute inflammatory pain response. Intrathecal roscovitine administration attenuates formalin-induced nociceptive responses and there is potential for further application.
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This work was supported by research grants from the Chang Gung Memorial Hospital (CMRPG- 83027, 83030, and 83033).
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Wang, Ch., Chou, Wy., Hung, Ks. et al. Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats. Acta Pharmacol Sin 26, 46–50 (2005). https://doi.org/10.1111/j.1745-7254.2005.00007.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00007.x
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