Correlations between edema and the immediate and prolonged painful consequences of inflammation: therapeutic implications?

The precise relationship between the degree of pain and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of an anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between-group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the injected paw (P< or =0.003), and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose tested (P< 0.05). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determining which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.