Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans.
To investigate the mechanism of vincristine-induced pain in humans undergoing chemotherapy we have established a model of vincristine-induced hyperalgesia in rat. Vincristine (100 micrograms/kg) was administered daily over a period of two weeks. An acute dose-dependent decrease in mechanical nociceptive threshold and an increased response to non-noxious mechanical stimuli ("hyperalgesia") occurred after the second day of administration. Chronic lowered threshold and increased response to stimuli (determined 24 h after each injection) was first noted during the second week of vincristine administration. Responses gradually returned to baseline during the two weeks following discontinuation of treatment. Vincristine also increased sensitivity to heat stimulation. At a dose that produced hyperalgesia (100 micrograms/kg), vincristine did not cause a significant motor deficit. Peripheral administration of a mu-opioid agonist did not reduce vincristine-induced acute hyperalgesia. Hyperalgesia induced by vincristine in the rat provides a good model for the experimental study of painful peripheral neuropathies in human patients receiving vincristine as a chemotherapeutic agent.
Aley
K O
KO
Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Reichling
D B
DB
Levine
J D
JD
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000633:toxicity*; D004195:Disease Models, Animal; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010812:Physical Stimulation; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014750:Vincristine / Q000009:adverse effects / Q000633:toxicity*
D000700:Analgesics; D000972:Antineoplastic Agents, Phytogenic; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D014750:Vincristine