title: Preclinical evidence for the antihyperalgesic activity of CDP-choline in oxaliplatin-induced neuropathic pain.
abstract: OBJECTIVE
  This study was designed to evaluate the antihyperalgesic effect of CDP-choline (cytidine-5'-diphosphate- choline; citicoline) in a rat model of neuropathic pain produced by oxaliplatin (OXA).
  
  
  METHODS
  A single administration of OXA (6 mg/kg intraperitoneally/ ip) was used for induction of neuropathy. We assessed the antihyperalgesic effect of intracerebroventricularly (icv) administered CDP-choline (0.5, 1.0 and 2.0 μmol) using the rat paw pressure test (Randall-Selitto).
  
  
  RESULTS
  CDP-choline significantly reduced OXA-induced mechanical hyperalgesia, in a dose- and time-dependent manner. The antihyperalgesic effect of CDP-choline was blocked by the neuronal high affinity choline uptake inhibitor hemicholinium-3 (1 μg; icv), the nonselective nicotinic receptor antagonist mecamylamine (50 μg; icv), the α7 selective nicotinic acetylcholine receptor antagonist α-bungarotoxin (2 μg; icv), and the gamma-amino butyric acid (GABA)-B receptor antagonist CGP-35348 (20 μg; icv), but not by the nonselective opioid receptor antagonist naloxone (10 μg; icv) and the nonselective muscarinic receptor antagonist atropine (10 μg; icv).
  
  
  CONCLUSIONS
  These findings indicate that CDP-choline exerts an antihyperalgesic effect in OXA-induced neuropatic pain and it can be tested in clinical trials.
authors.forename: O
authors.initials: O
authors.lastname: Kanat
authors.affiliation: Department of Medical Oncology, Uludag University Faculty of Medicine, Bursa, Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Kanat
authors.forename: D
authors.initials: D
authors.lastname: Bagdas
authors.forename: H Y
authors.initials: HY
authors.lastname: Ozboluk
authors.forename: M S
authors.initials: MS
authors.lastname: Gurun
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007276:Injections, Intraventricular; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000700:Analgesics; D058788:GABA-B Receptor Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D018733:Nicotinic Antagonists; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003566:Cytidine Diphosphate Choline