Behavioral and pharmacological description of oxaliplatin-induced painful neuropathy in rat.
We describe an animal model of nociceptive sensory neuropathy induced by repeat intravenous administration of oxaliplatin in which treated animals partly reproduce the characteristic pain symptoms in oxaliplatin-treated patients. We tested the ability of 1, 2 and 4 mg/kg oxaliplatin doses injected twice-weekly for four-and-a-half consecutive weeks to induce a nociceptive peripheral neuropathy in male Sprague-Dawley rats. The behavioral assessment revealed cold allodynia (10 degrees C) and hyperalgesia (4 degrees C) symptoms associated with a mechanical allodynia. The rats maintained a good general clinical status without motor dysfunction. The 2mg/kg oxaliplatin dose and the tail-immersion test in cold water (10 degrees C) were selected to compare pharmacological sensitivity between single administered drugs as morphine, lidocaine, carbamazepine, gabapentin and repeated administration of drugs as clomipramine, venlafaxine, calcium and magnesium solutions. Magnesium solution (90 mg/kg) and venlafaxine (7.5 mg/kg) administration induced an antinociceptive effect whereas gabapentin (300 mg/kg), clomipramine (2.5 mg/kg) and lidocaine (3 and 6 mg/kg) only induced an antiallodynic effect.
Ling
Bing
B
Université Clermont1, Faculté de Pharmacie, Laboratoire de Toxicologie, F63001 Clermont-Ferrand, France INSERM, U766, Faculté de Médecine et de Pharmacie, F63001 Clermont-Ferrand, France CHU Clermont-Ferrand, Service de Pharmacologie, Hopital G. Montpied, F-63003 Clermont-Ferrand, France.
Authier
Nicolas
N
Balayssac
David
D
Eschalier
Alain
A
Coudore
François
F
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin