ANTINOCICEPTIVE PROPERTIES OF PROTEIN-C IN A MODEL OF INFLAMMATORY HYPERALGESIA IN RATS

We investigated the role of human protein C in an animal model of infl ammatory hyperalgesia. Pain was induced by intraplantar injection of c arrageenan (3 mg) into the hind paw of rats. The pain threshold was me asured by exerting increasing amounts of pressure (in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg) was a dministered intravenously immediately after carrageenan. Controls rece ived either intraplantar injections of saline (100 mu l) instead of ca rrageenan or carrageenan alone. Effects on pain threshold were express ed in percent of the pretreatment value. Carrageenan alone lowered the mean pain threshold after 3 h to 33.2 +/- 2.2% of the pre treatment l evel. Addition of protein C resulted in a dose-dependent rise in pain threshold towards the level observed in control animals treated with s aline instead of carrageenan (pain threshold after 800 IU/kg protein C = 62.9 +/- 2.3% of pretreatment level), demonstrating an antinocicept ive effect. Protein C had no effect in animals not preconditioned with intraplantar carrageenan. Thus protein C clearly antagonized the infl ammatory pain induced by carrageenan. The antinociceptive action of pr otein C was antagonized by injection of a monoclonal antibody against protein C, providing additional evidence that the effect was protein C -mediated.