Preprodynorphin (PPD)-like immunoreactive (-LI) neuronal cell bodies in the trigeminal sensory nuclear complex of the rat were found in laminae I and II of the medullary dorsal horn (MDH; caudal spinal trigeminal nucleus) and the paratrigeminal nucleus. A PPD immunofluorescence histochemistry combined with a fluorescence retrograde tract-tracing method revealed that some of the PPD-LI neurons in the MDH and paratrigeminal nucleus projected to the thalamic regions. Nociceptive nature of the PPD-LI MDH neurons projecting to the thalamic regions was also demonstrated by a triple labeling method, using the technique of the noxious stimulus-evoked expression of the immediate-early gene, c-fos. In the rats which were subcutaneously injected with formalin into the upper and lower lips, c-fos protein (Fos) was found in PPD-LI neurons which were labeled with a retrograde tracer injected into the thalamic regions.