Original Article

Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats1

Cheng-haung WANG, Wen-ying CHOU, Kung-sheng HUNG, Bruno JAWAN, Cheng-nann LU, Jong-kang LIU, Yi-ping HUNG, Tsung-hsing LEE


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 M r 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