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

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 (iev) 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 a7 selective nicotinic acetylcholine receptor antagonist a-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 pg; 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.