The participation of pedunculopontine tegmental nucleus in descending pain control mechanisms has been proposed. The aim of this study was to investigate NADPH-d and c-Fos reactivity in the pedunculopontine tegmental nucleus following noxious peripheral stimulation. Formalin induced hind paw inflammation in the rat resulted in bilateral increase of Fos and NADPH-d expression in the pedunculopontine tegmental nucleus. Approximately 30% of labelled cells were double-labelled. Close proximity to NADPH-d labelled neuronal processes with Fos-labelled nuclei were observed. This anatomical relationship supports the hypothesis that pedunculopontine tegmental nucleus is involved in pain modulation and proposes a new explanation for the presence of nitric oxide in this nucleus.