Endothelial cells play an essential role in the thermal hyperalgesia induced by nerve growth factor

P A Foster, S K Costa, R Poston, J R Hoult, S D Brain

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Nerve growth factor (NGF) is a potent mediator of inflammatory hyperalgesia, in addition to roles in the development and maintenance of neurons. We provide evidence for the novel concept that microvascular endothelial cells play a critical primary role in NGF-mediated events that lead to inflammatory hyperalgesia in rat skin. We show that, surprisingly, neutrophils are not directly activated by NGF, although local administration of NGF mediates thermal hyperalgesia via mechanisms involving concomitant neutrophil accumulation. The co-administration of actinomycin D with NGF negated both neutrophil accumulation and thermal hyperalgesia, indicating the dependence of NGF on local de novo protein synthesis. More significantly, an antibody against the endothelial-derived adhesion molecule ICAM-1 also blocked neutrophil accumulation and thermal hyperalgesia. Finally the ability of NGF to stimulate ICAM-1 in human cultured umbilical vein endothelial cells is shown. We propose that NGF acts primarily to activate endothelial cells and that this response is essential for the ensuing neutrophil accumulation and hyperalgesia. The findings reveal a central role of the endothelial cell in initiating NGF-dependent inflammatory hyperalgesia and emphasize the importance of further investigations aimed at examining the feasibility of new therapeutic strategies that target NGF.
Original languageEnglish
Pages (from-to)1703 - 1705
Number of pages3
JournalTHE FASEB JOURNAL : OFFICIAL PUBLICATION OF THE FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY
Volume17
Issue number12
DOIs
Publication statusPublished - Sept 2003

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