Summary
We investigated the role of human protein C in an animal model of inflammatory hyperalgesia.
Pain was induced by intraplantar injection of carrageenan (3 mg) into the hind paw
of rats. The pain threshold was measured by exerting increasing amounts of pressure
(in mmHg) on the paw until a struggle reaction was observed. Protein C (8-800 IU/kg)
was administered intravenously immediately after carrageenan. Controls received either
intraplantar injections of saline (100 µ1) instead of carrageenan or carrageenan alone.
Effects on pain threshold were expressed in percent of the pretreatment value. Carrageenan
alone lowered the mean pain threshold after 3 h to 33.2 ± 2.2% of the pretreatment
level. Addition of protein C resulted in a dose-dependent rise in pain threshold towards
the level observed in control animals treated with saline instead of carrageenan (pain
threshold after 800 IU/kg protein C = 62.9 ± 2.3% of pretreatment level), demonstrating
an antinociceptive effect. Protein C had no effect in animals not preconditioned with
intraplantar carrageenan. Thus protein C clearly antagonized the inflammatory pain
induced by carrageenan. The antinociceptive action of protein C was antagonized by
injection of a monoclonal antibody against protein C, providing additional evidence
that the effect was protein C-mediated.
