c-fos antisense oligodeoxynucleotide increases formalin-induced nociception and regulates preprodynorphin expression.
Rats, receiving an intrathecal pretreatment of oligodeoxynucleotide complementary to c-fos mRNA (antisense), showed no increases in Fos protein or preprodynorphin messenger RNA in the outer laminae of the lumbar spinal cord when challenged 4 h later with a 50 microliters intraplantar injection of 5% formalin. Animals pretreated with saline or sense oligodeoxynucleotide showed marked increases in Fos protein (2 h after formalin challenge) and preprodynorphin mRNA (20 h after formalin challenge) in the lumbar region of the cord ipsilateral to the side of the injection. The behavioural consequences of antisense pretreatment were an increase in the formalin-induced licking/biting responses during the tonic, but not the acute phase. These observations could be interpreted as representing a sequence of events beginning with the formalin-induced increase in the transcription factor Fos, which in turn increases the synthesis of preprodynorphin messenger RNA resulting in the production of the dynorphin opioid peptides which then exert a modulatory antinociceptive action.
Hunter
J C
JC
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, U.K.
Woodburn
V L
VL
Durieux
C
C
Pettersson
E K
EK
Poat
J A
JA
Hughes
J
J
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002766:Cholecystokinin / Q000096:biosynthesis; D004399:Dynorphins / Q000096:biosynthesis*; D005557:Formaldehyde; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011498:Protein Precursors / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D016376:Oligonucleotides, Antisense; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C036448:pre-prodynorphin; D005557:Formaldehyde; D004399:Dynorphins; C042082:preprocholecystokinin; D002766:Cholecystokinin