Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia

Abstract

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 (0.1mg/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 58.02mN, skin compression 1.3 and 3N, 1mm(2)), increased acute A- and C-fiber responses, after-discharges and abnormal 'wind-up' to electrical stimuli (5mA, 2ms) at 0.1Hz 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.