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

We examined the effects of intrathecally preadministered injections of a phosphorothioate analog of c-fos antisense and mismatch oligodeoxynucleotides (ODNs) on the withdrawal latency to a thermal stimulus following unilateral injection of complete Freund's adjuvant (CFA) into the hind footpad of rats. Pretreatment with the c-fos antisense ODN significantly decreased the CFA-induced expression of c-Fos protein dose-dependently in ipsilateral laminae 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 mismatch ODN (63.6+/-2.9; 60.6+/-4.0) or saline (56.6+/-5.5). Animals pre-treated with 25 nM of the c-fos antisense ODN significantly increased the withdrawal latency to the noxious thermal stimulation (63.0-70.5%; compared with contralateral to the CFA injection) compared with animals pretreated with mismatch ODN (28.5-42.6%) or saline (26.4-45.3%) from 0 to 5 h after unilateral injection of CFA into the hind footpad. Pretreatment with 10 nM antisense ODN had a less significant effect. These results indicate that the expression of CFA-induced c-Fos in the dorsal horn might facilitate thermal nociception.