1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute in¯ammation, carrageenan-induced paw údema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw údema) and high doses (hyperalgesia). COX-2 and prostaglandin E 2 (PGE 2 ) levels were measured by RT ± PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a signi®cant and parallel induction of both COX-2 and PGE 2 . This induction was signi®cantly higher in hyperalgesia than in paw údema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and in¯ammatory cells of rats experiencing hyperalgesia. In paw údema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw údema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw údema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.

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