C-FOS ANTISENSE OLIGODEOXYNUCLEOTIDE INCREASES FORMALIN-INDUCED NOCICEPTION AND REGULATES PREPRODYNORPHIN EXPRESSION

Rats, receiving an intrathecal pretreatment of oligodeoxynucleotide co mplementary to c-fos mRNA (antisense), showed no increases in Fos prot ein or preprodynorphin messenger RNA in the outer laminae of the lumba r spinal cord when challenged 4 h later with a 50 mu l intraplantar in jection of 5% formalin. Animals pretreated with saline or sense oligod eoxynucleotide showed marked increases in Fos protein (2 h after forma lin challenge) and preprodynorphin mRNA (20 h after formalin challenge ) in the lumbar region of the cord ipsilateral to the side of the inje ction. The behavioural consequences of antisense pretreatment were an increase in the formalin-induced licking/biting responses during the t onic, but not the acute phase. These observations could be interpreted as representing a sequence of events beginning with the formalin-indu ced increase in the transcription factor Fos, which in turn increases the synthesis of preprodynorphin messenger RNA resulting in the produc tion of the dynorphin opioid peptides which then exert a modulatory an tinociceptive action.