Description of a short-term Taxol-induced nociceptive neuropathy in rats.
This work describes a new animal model of neuropathic pain produced by the single intraperitoneal administration of Taxol (32 mg/kg) to male Sprague-Dawley rats. During the course of the experiment, the clinical status of the rats remained satisfactory and motor function was not altered. A number of classical behavioural tests of nociception as well as histological and electrophysiological investigations were performed. Taxol administration produced an important and rapidly developing mechanical hyperalgesia, a thermal hypoalgesia but no mechanical or thermal allodynia. Degenerative changes were observed in the sciatic nerve, the nerve fibres in the paw subcutaneous tissue and in the lumbar spinal cord. When Taxol or vehicle (a mix of Cremophor and ethanol) were repeatedly injected once a week for 5 weeks, similar nociceptive disorders were observed in addition to a decrease in peripheral nerve conduction velocity. The selective dysfunction of high-diameter myelinated fibres observed after one single administration of Taxol (32 mg/kg) may be attributable to paclitaxel-induced neuropathy, however other mechanisms causing neurochemical dysfunction must also be involved.
Authier
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Laboratoire de Toxicologie, Faculté de Pharmacie, Equipe NeuroPsychoPharmacologie Université d'Auvergne (INSERM EMI 9904), 28 Place H. Dunant, BP 38, 63001 Clermont-Ferrand, France.
Gillet
J P
JP
Fialip
J
J
Eschalier
A
A
Coudore
F
F
D000818:Animals; D006197:Hair; D018737:Hand Strength; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D009431:Neural Conduction / Q000187:drug effects; D009437:Neuralgia / Q000139:chemically induced / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D017239:Paclitaxel / Q000633:toxicity*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D020886:Somatosensory Disorders / Q000139:chemically induced / Q000503:physiopathology*
D017239:Paclitaxel