The sensitization of peripheral nociceptors by different prostaglandins was studied in an in vitro preparation of the neonatal spinal cord with functionally attached tail. Nociceptors in the rat tail were activated by chemical (bradykinin, capsaicin) and thermal (heated saline) stimuli and responses were recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by bradykinin, capsaicin or submaximal thermal stimulation were enhanced in the presence of prostaglandin E1, prostaglandin E2, prostaglandin F2 alpha, prostaglandin I2 and the stable prostaglandin I2 analogue cicaprost, but not by prostaglandin D2. Cyclic AMP and threshold concentrations of bradykinin also induced an enhancement of responses to chemical and thermal stimuli. Responses evoked by small concentrations of bradykinin on unsensitized preparations were reduced by indomethacin or aspirin, whereas responses to maximal concentrations of bradykinin were not affected. Immunocytochemical localization of protein gene product 9.5 and growth associated protein 43 indicated that the neuronal innervation of subepidermal skin layers was preserved in the tail following removal of the most superficial skin layers which was performed in order to facilitate drug access to peripheral nerve endings. These results indicate that different prostaglandins and cyclic AMP sensitize peripheral nerve endings to noxious stimulation without directly activating nociceptors. The stimulation of nociceptors by bradykinin was only partially mediated via arachidonic acid metabolites whereas bradykinin-induced sensitization was independent of cyclo-oxygenase activity.