PENTOBARBITAL PREVENTS THE DEVELOPMENT OF C-FIBER-INDUCED HYPERALGESIA IN THE RAT

Noxious stimuli applied to the skin can produce long-lasting, C-fiber-dependent, secondary hyperalgesia that is mediated by central mechanisms. NMDA receptor antagonists and low doses of morphine can preferentially block the development of hyperalgesia without significantly altering unpotentiated responses to nociceptive stimuli. The aim of our study was to determine if low doses of pentobarbital can also preferentially alter either hyperalgesic or unpotentiated responses to nociceptive heat stimuli in spinalized and intact rats. Our results demonstrate the following. (1) Mustard oil applied above the ankle joint or electrical stimulation of the sciatic nerve at C-fiber intensity in spinalized, unanesthetized rats decreased the latency to withdrawal of the foot from water maintained at 47-49 degrees C. This secondary hyperalgesia to thermal stimulation persisted for at least 1 h and was most likely mediated by central mechanisms. (2) Pentobarbital in both spinalized and spinal cord-intact rats prevented the development of the late component (42-120 min) but only partially decreased the early (2-6 min) component of hyperalgesia. In contrast, pentobarbital had relatively minimal effects on unpotentiated withdrawal responses. Thus, pentobarbital is similar to morphine in its ability to prevent hyperalgesia, but may differ from the anesthetic isoflurane, which does not interfere with the development of hyperalgesia.