Journal
PAIN
Volume 103, Issue 1-2, Pages 131-138Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/S0304-3959(02)00445-1
Keywords
sensory processing; vincristine-induced hyperalgesia; allodynia; neuropathy; cancer
Categories
Funding
- NINDS NIH HHS [NS-39933] Funding Source: Medline
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Abnormal sensation and pain are major dose-limiting factors in cancer chemotherapy with vincristine. In this study, we have adapted a model of this condition by using repeated daily intraperitoneal injections of vincristine in rats. Mechanical allodynia and hyperalgesia without change in responses to thermal stimuli were first observed following 5-8 days of vincristine treatment (0.1 mg/kg/day) and then persisted throughout the remainder of the treatment interval (2-3 weeks). Electrophysiological recording from wide dynamic range (WDR) neurons in the lumbar (L4-L5) spinal dorsal horn in hyperalgesic rats demonstrated significantly increased spontaneous activity and after-discharges to noxious mechanical stimuli (von Frey filaments with a bending force greater than 58.02 mN, skin compression 1.3 and 3 N, 1 mm(2)), increased acute A-and C-fiber responses, after-discharges and abnormal 'wind-up' to electrical stimuli (5 mA, 2 ms) at 0.1 Hz applied across the receptive field. These results suggest a state of central sensitization develops in spinal WDR neurons with repeated vincristine treatment that contributes to the spontaneous pain and hyperalgesia seen in patients and the hyperresponsiveness to sensory stimuli seen in animals treated with vincristine. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
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