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C-phycocyanin (C-PC), a biliprotein found in blue green algae, such as Spirulina platensis, is often used as a dietary nutritional supplement due to its various therapeutic values. In addition, the antiinflammatory activity of C-PC partly through inhibition of proinflammatory cytokine formation, inducible nitric oxide synthase (iNOS) and cyclooxygeanase-2 (COX-2) expression has been demonstrated in many in vitro and in vivo studies. However, whether C-PC also has antihyperalgesic activity in inflammatory nociception has not been investigated.Using a carrageenan-induced thermal hyperalgesia model, we evaluated the effect of C-PC on nociception by measuring paw withdrawal latency. To clarify the mechanisms involved, the expression of iNOS and COX-2 and the formation of nitrate and tumor necrosis factor-α (TNF-α) in the rat paw were determined.Pre- or posttreatment with C-PC (30 or 50 mg/kg, IP) significantly attenuated carrageenan-induced inflammatory nociception and the induction of iNOS and COX-2 at the late phase, (4 h) accompanied by an inhibition of the formation of TNF-α, prostaglandin E2, nitrate and myeloperoxidase activity.Based on these results, it is suggested that the inhibition of NO and prostaglandin E2 over-production through suppressing iNOS and COX-2 induction and attenuation of TNF-α formation and neutrophil infiltration into inflammatory sites by C-PC may contribute, at least in part, to its antihyperalgesic activity.