Expression of Concern: Carrageenan‐induced mouse paw oedema is biphasic, age‐weight dependent and displays differential nitric oxide cyclooxygenase‐2 expression

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Abstract
Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7‐ or 8‐week old, weighing 32–34 g, displayed a consistent response in both phases. In 8‐week‐old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX‐2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX‐2 expression at 6 and 24 h in 3–8‐week‐old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX‐2 that is present only in the second phase of the oedema and is not linked to mouse age–weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX‐1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX‐1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age‐weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX‐1 and COX‐2 in response to carrageenan injection in the two phases of the mouse paw oedema. British Journal of Pharmacology (2004) 142, 331–338. doi:10.1038/sj.bjp.0705650