LOCAL INJECTION OF NERVE GROWTH-FACTOR (NGF) TRIGGERS DEGRANULATION OF MAST-CELLS IN RAT PAW

We examined the relationship between hyperalgesia and degranulation of mast cells in rats following treatment with nerve growth factor (NGF) and inflammatory mediators. Intracutaneous injection to the rat's paw of NGF (50-5000 ng, 50 mu l) evoked dose-dependent thermal hyperalges ia as measured by paw withdrawal latency to noxious heat. Even more in tense hyperalgesia was induced by an 'inflammatory mediators soup' con taining BK, 5HT, PGE2 and histamine (10 mu M). Counts of mast cells in the dermis were performed on coded slides under x 1000 magnification after fixation in Carnoy's solution and staining with toluidine blue. After injection of three different concentrations of NGF (50, 500, 500 0 ng in 50 mu l), the proportion of mast cells that were degranulated was significantly higher (P < 0.001) than after saline injection. No s ignificant differences were found among the three concentrations of NG F. The effect of inflammatory soup on the proportion of degranulated m ast cells was similar to that of NGF. These results indicate that NGF activates cutaneous mast cells and stimulates the release of inflammat ory tissue mediators in the acute phase of NGF-induced hyperalgesia in the rat's paw. However, the finding that degranulation was not dose-d ependent indicates that other mechanisms, independent of mast cells, a re probably operating in response to NGF. (C) 1997 Elsevier Science Ir eland Ltd.