The present study was designed to determine if nitric oxide (NO) was involved both in the dorsal horn responses to the primary nociceptive inputs and the descending inhibitory action on these responses. The first part of the experiments showed that when formalin was injected into one hindpaw, the nociceptive c-fos expression in the lumbar dorsal horn ipsilateral to the injection was suppressed dose-dependently by intrathecal (i.t.) administration of N-omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor. In the second part of the study, the formalin injection was carried out into two hindpaws of the rats with a sectioned dorsal quadrant at the thoracic spinal level, in these rats, there was a significant suppression of c-fos expression in the dorsal horn on the side with intact dorsal quadrant, reasonably owing to the preservation of the spinally descending inhibitory fibers from the supraspinal level; furthermore, this suppression could be canceled following i.t. L-NNA administration. The results suggest that endogenous NO not only facilitates the perception of nociceptive inputs at the spinal level but also enhances the descending inhibition upon the spinal nociception. (C) 1998 Elsevier Science Ireland Ltd.