The mechanism of action of prostaglandins (PGs) to sensitize sensory terminals to noxious stimuli was studied in the isolated spinal cord-tail preparation of the newborn rat. Application of a small amount of capsaicin to the tail induced a nociceptive reflex that was recorded extracellularly from the lumbar ventral root. Pretreatment of the tail with PGE1 or E2 (0.8-4 microM) markedly potentiated the capsaicin-induced nociceptive reflex. In the isolated spinal cord preparation of the newborn rat, application of PGE1 or E2 (10 nM-1 microM) induced a depolarization of the dorsal root. Based on these results we propose a hypothesis that PGs regulate the resting potential of the peripheral terminals of nociceptive primary afferent fibers and that the depolarization is associated with lowering of threshold for various noxious stimuli.