Open AccessIntrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin‐induced nociceptive response in rats
Author(s) -
WANG Chenghaung,
CHOU Wenying,
HUNG Kungsheng,
JAWAN Bruno,
LU Chengnann,
LIU Jongkang,
HUNG Yiping,
LEE Tsunghsing
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00007.x
Subject(s) - nociception , cyclin dependent kinase 5 , pharmacology , western blot , (+) naloxone , hyperalgesia , medicine , phosphoprotein , phosphorylation , chemistry , opioid , protein kinase a , receptor , mitogen activated protein kinase kinase , gene , biochemistry
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 application.