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.
Sugiyo
S
S
Department of Prosthetic Dentistry II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan.
Yonehara
N
N
Appenteng
K
K
Nokubi
T
T
Shigenaga
Y
Y
Takemura
M
M
D000818:Animals; D001522:Behavior, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000737:chemistry / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012018:Reflex
D020319:Oligodeoxyribonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D005620:Freund's Adjuvant