G. Bennett et al., NERVE GROWTH-FACTOR INDUCED HYPERALGESIA IN THE RAT HIND PAW IS DEPENDENT ON CIRCULATING NEUTROPHILS, Pain, 77(3), 1998, pp. 315-322
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.