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.

To investigate the role of immediate-early gene c-fos in sodium selenite-induced apoptosis and its position in a possible cascade of apoptogenic genes, we compared the time-courses of expression for 5 related genes, including c-fos, during the apop- tosis induced by sodium selenite with or without blockage of c-fos expression by adding c-fos antisense oligodeoxynucleotide ( ASO) in cultured cortical neurons. The results showed that: (1) in control experiments without c-fos ASO adding, 0. 5 μmol/ L sodium selenite-induced apoptosis as revealed by electrophoretic and flow cytometric examinations; at the same time, sodium selenite also induced down-regulation of bcl-2 mRNA expression and up-regulations of mRNAs related to bax, c-fos, p53, and acetylcholinesterase (AChE) genes; (2) in similar experimental conditions with c-fos ASO cotreatment, the sodium selenite-in- duced apoptosis was blocked with the up-regulation of p53 expression still emerging as before, while the changes in expressions of bcl-2, bax, AChE genes were reversed at the same time. The results suggest that c-fos ASO could play a protective role upon cortical neurons from suffering apoptosis induced by sodium selenite, and there might exist a cascade of gene expressions with p53 and c-fos genes being regulated upstream and then bcl-2, bax, and AChE genes being regulated downstream.