Abstract
BACKGROUND: Postoperative pain remains a significant problem despite optimal treatment with current drugs. Nonsteroidal antiinflammatory drugs reduce inflammation and provide analgesia but are associated with adverse side effects. METHODS: We tested low doses (0.5-5 mg/kg) of parenteral ketoprofen against pain-related behaviors after plantar incision in rats. To further evaluate the potential sites of action of ketoprofen in our model, a novel, sustained-release microparticle formulation of ketoprofen was placed into the wound, and tested for its effects on pain behaviors. Intrathecal ketoprofen (150 microg) was also studied. Plasma samples were assayed for drug concentrations. RESULTS: We found that low doses of parenterally administered ketoprofen produced a modality-specific effect on pain behaviors; guarding after incision was decreased, whereas no inhibition of exaggerated responses to heat or mechanical stimuli was evident. Very low doses, 0.5 mg/kg, could produce inhibition of guarding. The locally applied sustained-release ketoprofen-eluting microparticles and intrathecally administered ketoprofen also produced a modality-specific effect on pain behaviors after incision, inhibiting only guarding. Plasma levels of ketoprofen after parenteral or local administration were in the range of therapeutic blood levels in postoperative patients. CONCLUSIONS: This study demonstrates that ketoprofen is an effective analgesic for nonevoked guarding in rats after plantar incision. There was no effect on mechanical or heat responses, which highlights the importance of multiple-modality testing of pain behaviors for drug evaluation. We found efficacy at doses used clinically in postoperative patients.