Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats
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Published on: September 2, 2020
Cheng-haung Wang1, Wen-ying Chou, Kung-sheng Hung
1Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Kaoshiung 804, Taiwan, China.
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.
Insights
The cyclin-dependent kinase5 (Cdk5) inhibitor roscovitine effectively reduced pain responses in rats. This study suggests Cdk5 and DARPP-32 phosphorylation play roles in inflammatory pain pathways.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cyclin-dependent kinase5 (Cdk5) is implicated in pain signaling pathways.
- Understanding Cdk5's role in nociception is crucial for developing novel analgesics.
Purpose of the Study:
- To investigate the antinociceptive effects of roscovitine, a Cdk5 inhibitor, on formalin-induced pain in rats.
- To explore the involvement of Cdk5 and its downstream target, DARPP-32 phosphorylation, in inflammatory pain.
Main Methods:
- Formalin test in rats to induce nociceptive responses (flinch response).
- Intrathecal administration of roscovitine to assess dose-dependent effects.
- Western blot analysis to measure Cdk5 and phosphorylated DARPP-32 (p-DARPP-32) levels.
- Naloxone administration to investigate opioid receptor involvement.
Main Results:
- Roscovitine significantly suppressed formalin-induced flinching in a dose-dependent manner.
- Formalin injection increased p-DARPP-32 levels, an effect reversed by roscovitine.
- Roscovitine's antinociceptive effect was partially blocked by naloxone, suggesting opioid pathway interaction.
Conclusions:
- DARPP-32 phosphorylation is involved in the acute inflammatory pain response.
- Intrathecal roscovitine exhibits antinociceptive properties against formalin-induced pain.
- Cdk5 inhibition presents a potential therapeutic strategy for inflammatory pain management.
