Inhibition of carrageenan-induced edema by indomethacin or sodium salicylate does not prevent the increase of nerve growth factor in the rat hind paw

It is known that the concentration of nerve growth factor (NGF) is increased in inflamed tissue, a phenomenon thought to induce long-lasting sensitization of afferent neurons. Although the effects of NGF may be of pathophysiological relevance, there is little known about the effects of non-steroidal anti-inflammatory drugs on the inflammation-induced increase in NGF. In the present study, therefore, we used the non-steroidal anti-inflammatory drugs indomethacin and sodium salicylate in carrageenan-induced rat paw inflammation, in order to compare their anti-inflammatory action (determined as inhibition of edema) with their effects on the concentration of NGF in inflamed tissue. Carrageenan induced inflammation increased the concentration of NGF in the paw 2-fold compared to non-inflamed controls. Indomethacin (0.66-2 mg/kg) and sodium salicylate (100-300 mg/kg) inhibited carrageenan-induced paw edema and indomethacin also inhibited the ex-vivo release of immunoreactive prostaglandin E-2 from inflamed paw skin. However, at these doses, neither anti-inflammatory agent reduced the elevated levels of NGF. In contrast, a supramaximal dose of indomethacin (6 mg/kg) partially inhibited, and dexamethasone completely prevented the carrageenan-induced increase in NGF. These results suggest that the anti-inflammatory potency of drugs as determined in the carrageenan edema model is not necessarily predictive for their ability to inhibit the NGF response. it seems possible, therefore, that even if anti-inflammatory treatment prevents the appearance of visible signs of inflammation, there may be still long-lasting effects of NGF on the phenotype of primary afferent neurons. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.