Hou Wy

Intrathecally administered c-fos antisense oligodeoxynucleotide decreases formalin-induced nociceptive behavior in adult rats

c-fos antisense strategy was applied as a pharmacological approach to characterize its dose-dependent role and reversibility in the reduction of formalin-induced hyperalgesia. Nociceptive behavioral responses (weighted score, flinching response, licking/biting) following formalin (50 microl 5%) injection were assessed in adult Wistar rats receiving different doses (50 nM, 250 nM) of intrathecally administered c-fos antisense oligodeoxynucleotides at different times prior to formalin injections. The treatments dose dependently decreased both Fos immunoreactivity expression in dorsal horn of rat lumbar spinal cord and all nociceptive measures in the tonic phase of the formalin test. c-Fos correlated well with weighted pain score and/or flinching responses, but not with licking/biting behavior. With the exception of a 48-120 h period required for licking/biting behavior to be restored to its normal status, the suppressive effect on c-fos expression and other nociceptive behaviors disappeared 48 h following c-fos antisense oligodeoxynucleotide treatment. The results suggest a pharmacological potential of c-fos antisense oligodeoxynucleotides in the central nervous system to block immediate-early genes and their resulting physiological consequence following noxious stimulus.

Protein synthesis inhibitor cycloheximide dose-dependently decreases formalin-induced c-Fos protein and behavioral hyperalgesia in rats

We had previously demonstrated that c-fos antisense oligodeoxynucleotides dose-dependently suppressed formalin-induced c-Fos protein and behavioral hyperalgesia. To test whether de novo protein synthesis is required for the development of persistent pain after peripheral inflammation, we observed formalin-induced spinal c-Fos protein and nociceptive behaviors following pretreatment with cycloheximide, a protein synthesis inhibitor. Cycloheximide dose-dependently inhibited formalin-induced spinal c-Fos protein and tonic nociceptive responses. The possible non-specific effects other than protein synthesis inhibition on nociceptive behavior were carefully discussed and excluded. These results provide further support to the hypothesis that de novo protein synthesis is essential for the development of behavioral hyperalgesia.