Behavioral and pharmacological description of oxaliplatin-induced painful neurop

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Pain. 2006 Nov 3

Behavioral and pharmacological description of oxaliplatin-induced

painful neuropathy in rat.

Ling B, Authier N, Balayssac D, Eschalier A, Coudore F.

Universite Clermont1, Faculte de Pharmacie, Laboratoire de

Toxicologie, F63001 Clermont-Ferrand, France; INSERM, U766, Faculte

de Medecine et de Pharmacie, F63001 Clermont-Ferrand, France.

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

4mg/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 (90mg/kg) and venlafaxine (7.5mg/kg)

administration induced an antinociceptive effect whereas gabapentin

(300mg/kg), clomipramine (2.5mg/kg) and lidocaine (3 and 6mg/kg)

only induced an antiallodynic effect.