title: Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Kaoshiung 804, Taiwan, China.
authors.forename: Cheng-haung
authors.initials: CH
authors.lastname: Wang
authors.forename: Wen-ying
authors.initials: WY
authors.lastname: Chou
authors.forename: Kung-sheng
authors.initials: KS
authors.lastname: Hung
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.forename: Cheng-nann
authors.initials: CN
authors.lastname: Lu
authors.forename: Jong-kang
authors.initials: JK
authors.lastname: Liu
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Hung
authors.forename: Tsung-hsing
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000818:Animals; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005557:Formaldehyde / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011687:Purines; D000077546:Roscovitine; D005557:Formaldehyde; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases