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 hyperalgesia 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 accumulation was measured in hind paw and dorsal skin samples using a myeloperoxidase assay. NGF (23-80 pmol intraplantar (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-1beta 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.
Bennett
G
G
Pharmacology Group and Vascular Biology Research Centre, King's College, Manresa Road, London SW3 6LX, UK.
Al-Rashed
S
S
Hoult
S J R
SJR
Brain
D S
DS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D006614:Hindlimb; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000276:immunology*; D015289:Leukotrienes / Q000276:immunology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D008784:Methysergide / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D009619:Nociceptors / Q000276:immunology; D017288:Pain Threshold / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D011714:Pyrans / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018490:Serotonin Agents / Q000494:pharmacology; D012867:Skin / Q000201:enzymology / Q000294:innervation
D000906:Antibodies; D006634:Histamine H1 Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009414:Nerve Growth Factors; D011714:Pyrans; D015363:Quinolones; D018490:Serotonin Agents; C088450:ZM 230487; D009195:Peroxidase; D011738:Pyrilamine; D008784:Methysergide