Effect of colchicine on nerve growth factor-induced leukocyte accumulation and thermal hyperalgesia in the rat.

In addition to its neuronal effects, nerve growth factor (NGF) is known to act on inflammatory and immune cells. The aim of the present study was to investigate the effect of colchicine on NGF-induced leukocyte accumulation and thermal hyperalgesia. Initial experiments showed that intradermal injection of recombinant human (rh) NGF (0.8 and 4 microg) caused a longlasting increase in tissue myeloperoxidase (MPO) indicating leukotactic activity of NGF. Colchicine (0.3 and 1 mg/kg) attenuated the NGF (0.8 and 4 microg)-induced increase in tissue myeloperoxidase (MPO) as determined 6 h after NGF application. Intraplantar injection of NGF into the rat hindpaw caused a decrease in thermal nociceptive threshold, which, at 4 microg NGF, was accompanied by moderate (about 35% increase in paw volume) edema. The thermal hyperalgesia was evident 20 min after injection and lasted less than 4 h. Colchicine (0.3 and 1 mg/kg) had no significant effect on NGF-induced edema, but reduced NGF-induced thermal hyperalgesia. Colchicine (1 mg/kg) did not significantly reduce thermal hyperalgesia produced by intraplantar bradykinin, prostaglandin E1, or 5-hydroxytryptamine. Treatment of rats with a dose of indometacin (2 mg/kg) that was sufficient to block cyclooxygenase had no significant effect on NGF-induced thermal hyperalgesia or edema. In vitro, colchicine (0.4-12 microg/ml) did not significantly influence NGF (10 ng/ml)-induced histamine release from rat peritoneal cells, suggesting that a mast cell stabilizing effect of colchicine did not contribute to inhibition of NGF-induced thermal hyperalgesia. The results show that NGF causes localized indometacin-resistant thermal hyperalgesia that can be blocked by the microtubule disrupting agent colchicine. These results raise the possibility that a mechanism by which NGF produces peripheral sensitization is related to its leukotactic effect.