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.
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Wang, C. H., Chou, W. Y., Hung, K. S., Jawan, B., Lu, C. N., Liu, J. K., Hung, Y. P., & Lee, T. H. (2005). Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive in rats. Acta Pharmacologica Sinica, 26(1), 46-50. https://doi.org/10.1111/j.1745-7254.2005.00007.x