Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat.
The development of painful peripheral neuropathy is a dose-limiting side effect of numerous cancer chemotherapeutic agents. The present study utilized a rodent model of vincristine-induced neuropathy to determine whether a glial modulating agent, propentofylline, could attenuate vincristine-induced mechanical allodynia. Intravenous vincristine administered on days 1 through 5 and days 8 through 11 produced mechanical allodynia using 2 and 12 g von Frey filaments. Lumbar spinal cord from animals on day 15 expressed mild bilateral microglial and astrocytic activation as compared to saline-treated animals. Daily intraperitoneal propentofylline at 10 mg/kg attenuated mechanical allodynia induced by vincristine administration. In addition, propentofylline was found to decrease spinal microglial and astrocytic activation on day 15. These data suggest that central glial cells may play an important role in the development of painful neuropathy following vincristine administration.
Department of Pharmacology and Toxicology, Dartmouth Medical School, HB 7650, Hanover, NH 03755, USA. sweitzer@med.sc.edu
S M
SM
Sweitzer
J L
JL
Pahl
J A
JA
DeLeo
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004338:Drug Combinations; D006930:Hyperalgesia / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects*; D014970:Xanthines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D018696:Neuroprotective Agents; D014970:Xanthines; D014750:Vincristine; C032114:propentofylline