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

• 来源期刊: 中国药理学报（英文版）
• 关键词: roscovitine cyclin-dependent kinase-5 DARPP-32
• 年，卷（期）: 2005,（1）
• 页码范围: 46-50
• 页数: 5页
• 语种: 英文

摘要

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.