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

Cheng Haung Wang, Wen Ying Chou, Kung Sheng Hung, Bruno Jawan, Cheng Nann Lu, Jong Kang Liu, Yi Ping Hung, Tsung Hsing Lee

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)46-50
Number of pages5
JournalActa Pharmacologica Sinica
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 2005
Externally publishedYes

Keywords

  • Cyclin-dependent kinase-5
  • DARPP-32
  • Roscovitine

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology

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