Preclinical evidence for the antihyperalgesic activity of CDP-choline in oxaliplatin-induced neuropathic pain

J BUON. 2013 Oct-Dec;18(4):1012-8.

Abstract

Purpose: 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).

Conclusion: These findings indicate that CDP-choline exerts an antihyperalgesic effect in OXA-induced neuropatic pain and it can be tested in clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / pharmacology*
  • Animals
  • Cytidine Diphosphate Choline / administration & dosage
  • Cytidine Diphosphate Choline / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • GABA-B Receptor Antagonists / pharmacology
  • Hyperalgesia / chemically induced
  • Hyperalgesia / physiopathology
  • Hyperalgesia / prevention & control*
  • Injections, Intraventricular
  • Male
  • Neuralgia / chemically induced
  • Neuralgia / physiopathology
  • Neuralgia / prevention & control*
  • Neurotransmitter Uptake Inhibitors / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Organoplatinum Compounds*
  • Oxaliplatin
  • Pain Threshold / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Analgesics
  • GABA-B Receptor Antagonists
  • Neurotransmitter Uptake Inhibitors
  • Nicotinic Antagonists
  • Organoplatinum Compounds
  • Oxaliplatin
  • Cytidine Diphosphate Choline