A new animal model of vincristine-induced nociceptive peripheral neuropathy.
Using doses close to those used clinically, we have developed an animal model of vincristine-induced nociceptive sensory neuropathy after repeated intravenous injection in male Sprague-Dawley rats. In order to validate the model, three different doses (50, 100 and 150 microg/kg) of vincristine were injected every 2nd day until five injections had been given. The sensory behavioural assessment revealed mechanical hyperalgesia and allodynia associated with cold thermal hyperalgesia and allodynia. With regard to electrophysiological evaluation, we observed a decrease in the nerve conduction velocity in the highest dose group. Morphological studies revealed few degenerated fibers in the sciatic nerve and many degenerated myelinated axons in the fine nerve fibers of the subcutaneous paw tissue. Finally, to develop an animal model, we chose the 150 microg/kg dose because of the good general clinical status of the rats without motor function changes associated with severe sensation disorders like hyperalgesia and allodynia. This model of vincristine-induced painful neuropathy will be used to explore physiopathological mechanisms implied in the genesis of neuropathic pain and also to test new analgesic and neuroprotective drugs.
Authier
Nicolas
N
EMI INSERM/UdA 9904, Laboratoire de Toxicologie, Facultés de Médecine et Pharmacie, 28 Place H. Dunant-BP 38, 63001 Clermont-FERRAND, France. authier@hotmail.com
Gillet
Jean-Pierre
JP
Fialip
Joseph
J
Eschalier
Alain
A
Coudore
François
F
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D014750:Vincristine / Q000633:toxicity*
D014750:Vincristine