An animal model of nociceptive peripheral neuropathy following repeated cisplatin injections.
We report the assessment of motor and sensory behaviors using an electrophysiologic and an histologic approach, in a rat model of cisplatin peripheral neuropathy. Cisplatin was injected intraperitoneally one (3 mg/ kg), two (2 mg/kg), or three (1 mg/kg) times a week up to a cumulative dose of 15 or 20 mg/kg. With regard to nociceptive signs, we observed mechanical and thermal (cold stimuli) hyperalgesia and allodynia associated with minor motor disorders for the 3 mg/kg dose. Peripheral nerve conduction velocities were decreased in the cisplatin-(3 mg/kg) treated group. In addition, the histologic approach revealed that large axons were more frequently affected than the small ones, and nonmyelinated axons were unaffected. However, even in the most severe cases, myelin sheaths remained within normal limits. This animal model of nociceptive neuropathy would be suitable to study the pathophysiologic mechanisms of neuropathic pain and to test potential neuroprotective agents.
Authier
Nicolas
N
Laboratoire de Toxicologie, Facultés de Médecine et Pharmacie, EMI INSERM/UdA 9904, 28 place Henri Dunant, BP 38, 63001, Clermont-Ferrand, France.
Gillet
Jean Pierre
JP
Fialip
Joseph
J
Eschalier
Alain
A
Coudore
François
F
D000818:Animals; D000970:Antineoplastic Agents; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D002945:Cisplatin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018737:Hand Strength; D006358:Hot Temperature; D066298:In Vitro Techniques; D008161:Lumbosacral Region; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D010146:Pain / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology
D000970:Antineoplastic Agents; D002945:Cisplatin