Dexamethasone prevents the induction of COX-2 mRNA and prostaglandins in the lumbar spinal cord following intraplantar FCA in parallel with inhibition of oedema.
The inducible form of cyclo-oxygenase (COX-2) mRNA is rapidly induced in the spinal cord following peripheral inflammation produced by intraplantar injection of Freund's complete adjuvant (FCA). COX-2 mRNA induction is also accompanied by increased prostaglandin (PG) levels which are closely correlated with behavioural indicators of increased pain sensitivity. The aim of this study was to determine whether the anti-inflammatory glucocorticoid, dexamethasone, which acts locally to prevent the development of oedema would also reduce the associated central changes characterised by the induction of COX-2 mRNA and PGs. Unilateral intraplantar FCA induced a marked oedema evident from 2 h to 7 days after FCA injection which was significantly attenuated by dexamethasone pretreatment at all time points. Dexamethasone also significantly prevented the induction of COX-2 mRNA (2 4 h) and elevated levels of prostaglandins (6-keto PGF1alpha) in lumbar spinal cord (8 h). In this study we have confirmed the anti-inflammatory effect of dexamethasone and linked this to central changes in gene expression relevant to the development of altered pain thresholds following intraplantar FCA.
Department of Neuromuscular Diseases, Imperial College School of Medicine, Charing Cross Hospital, London, UK.
C H
CH
Hay
J S
JS
de Belleroche
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005620:Freund's Adjuvant; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D007278:Injections, Spinal; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007527:Isoenzymes; D011453:Prostaglandins; D012333:RNA, Messenger; D003907:Dexamethasone; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases