NERVE GROWTH-FACTOR INDUCED HYPERALGESIA IN THE RAT HIND PAW IS DEPENDENT ON CIRCULATING NEUTROPHILS

The mechanisms by which nerve growth factor (NGF) induces thermal hype ralgesia and neutrophil accumulation have been investigated in the rat . Thermal nociceptive thresholds in rat hind paw were measured as the time taken for paw withdrawal from a heat source and neutrophil accumu lation was measured in hind paw and dorsal skin samples using a myelop eroxidase assay. NGF (23-80 pmol intraplantar (i.pl.) injection) induc ed a significant (P < 0.05, n = 6-16) thermal hyperalgesia at 5 h afte r injection and significant neutrophil accumulation (P < 0.05, n = 6) was observed with NGF (40 pmol). In dorsal skin, where multiple sample s can be assessed, intradermal (i.d.) NGF was 10-30 times less potent than interleukin-1 beta in inducing neutrophil accumulation. The 5-lip oxygenase inhibitor ZM230487 (10 nmol co-injected with NGF) significan tly attenuated neutrophil accumulation and hyperalgesia induced by NGF ; unlike the histamine and 5-hydroxytryptamine antagonists (mepyramine and methysergide) which were without effect at the times measured. Fu rthermore, depletion of circulating neutrophils (using a rabbit anti-r at neutrophil antibody) abolished NGF induced hyperalgesia. These resu lts indicate that neutrophils, which accumulate in response to a 5-lip oxygenase product, play a crucial role in NGF-induced hyperalgesia. (C ) 1998 International Association for the Study of Pain. Published by E lsevier Science B.V.