Effects of intrathecal c-fos antisense oligodeoxynucleotide on adjuvant-induced thermal hyperalgesia

We examined the effects of intrathecally preadministered injections of a ph osphorothioate analog of c-fos antisense and mismatch oligodeoxynucleotides (ODNs) on the withdrawal latency to a thermal stimulus following unilatera l injection of complete Freund's adjuvant (CFA) into the hind footpad of ra ts. Pretreatment with the c-fos antisense ODN significantly decreased the C FA-induced expression of c-Fos protein dose-dependently in ipsilateral lami nae I/II (LI/II) of the dorsal horn (mean SEM per section: 10 nM ODN, 43.9 +/-1.3; 25 nM ODN, 19.4 +/-4.1) compared with pretreatment with the mismatc h ODN (63.6 +/-2.9; 60.6 +/-4.0) or saline (56.6 +/-5.5). Animals pre-treat ed with 25 nM of the c-fos antisense ODN significantly increased the withdr awal latency to the noxious thermal stimulation (63.0-70.5%; compared with contralateral to the CFA injection) compared with animals pretreated with m ismatch ODN (28.5-42.6%) or saline (26.4-45.3%) from 0 to 5 h after unilate ral injection of CFA into the hind footpad. Pretreatment with 10 nM antisen se ODN had a less significant effect. These results indicate that the expre ssion of CFA-induced c-Fos in the dorsal horn might facilitate thermal noci ception.