Ed in hind paw and dorsal skin samples using a myeloperoxidase assay. NGF (23–80 pmol intra-plantar (i.pl.) injection) induced a significant (P<0.05, n=6–16) thermal hyperalgesia at 5 h after injection and significant neutrophil accumulation (P<0.05, n=6) was observed with NGF (40 pmol). In dorsal skin, where multiple samples can be assessed, intradermal (i.d.) NGF was 10–30 times less potent than interleukin-1β in inducing neutrophil accumulation. The 5-lipoxygenase inhibitor ZM230487 (10 nmol co-injected with NGF) significantly 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. Furthermore, depletion of circulating neutrophils (using a rabbit anti-rat neutrophil antibody) abolished NGF induced hyperalgesia. These results indicate that neutrophils, which accumulate in response to a 5-lipoxygenase product, play a crucial role in NGF-induced hyperalgesia....