By using intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against preprodynorphin mRNA in rats, we observed that this treatment could block both the formalin-induced behavioral nociceptive responses and the increased expression of dynorphin A (1-8) in the dorsal horn, with the increased expression of c-Fos protein being unchanged. For we have reported that intrathecal administration of AS-ODN against c-fos mRNA blocks the nociceptive responses and both the increased Fos protein and dynorphin A (1-8), the results of the present study suggest that: (1) Nociceptively induced spinal expression of dyorphin and Fos protein is involved in the transmission of nociceptive information at the spinal level and the expression of Fos protein is the up-stream event. (2) dynorphin may act as a pronociceptive, not an antinociceptive, factor in the modulation of the spinal hyperalgesic state.