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

2005; Springer Nature; Volume: 26; Issue: 1 Linguagem: Inglês

10.1111/j.1745-7254.2005.00007.x

1745-7254

Cheng-Haung Wang, Wen‐Ying Sylvia Chou, Kung-sheng HUNG, Bruno Jawan, Cheng-nann LU, Jong-Kang Liu, Yi-Ping Hung, Tsung-Hsing Lee,

Pharmacological Effects of Natural Compounds

To investigate effects of the cyclin-dependent kinase5 (Cdk5) inhibitor roscovitine on formalin-induced nociceptive responses in rats. 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. 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. 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.