Present address: Department of Biology, American University of Beirut, Beirut, Lebanon
Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor α
Article first published online: 10 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 121, Issue 3, pages 417–424, May 1997
How to Cite
Woolf, C. J., Allchorne, A., Safieh-Garabedian, B. and Poole, S. (1997), Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor α. British Journal of Pharmacology, 121: 417–424. doi: 10.1038/sj.bjp.0701148
- Issue published online: 10 FEB 2009
- Article first published online: 10 FEB 2009
- (Received January 17, 1997, Accepted February 24, 1997)
- nerve growth factor;
- tumour necrosis factor;
Peripheral inflammation is characterized by heightened pain sensitivity. This hyperalgesia is the consequence of the release of inflammatory mediators, cytokines and growth factors. A key participant is the induction of the neurotrophin nerve growth factor (NGF) by interleukin-1β (IL-1β).
Tumour necrosis factor α (TNFα) has been shown both to produce hyperalgesia and to upregulate IL-1β. We have now examined whether the induction of TNFα in inflammatory lesions contributes to inflammatory sensory hypersensitivity by inducing IL-1β and NGF.
The intraplantar injection of complete Freund's adjuvant (CFA) in adult rats produced a localized inflammation of the hindpaw with a rapid (3 h) reduction in withdrawal time in the hot plate test and in the mechanical threshold for eliciting the flexion withdrawal reflex.
The CFA-induced inflammation resulted in significant elevation in the levels of TNFα, IL-1β and NGF in the inflamed paw. In the case of TNFα, an elevation was detected at 3 h, rose substantially at 6 h, peaked at 24 h and remained elevated at 5 days, with similar but smaller changes in the contralateral non-inflamed hindpaw. No increase in serum TNFα was detected at 24 h post CFA injection.
Intraplantar recombinant murine TNFα injections produce a short-lived (3–6 h) dose-dependent (50–500 ng) increase in thermal and mechanical sensitivity which was significantly attenuated by prior administration of anti-NGF antiserum.
Intraplantar TNFα (100–500 ng) also elevated at 6 but not 48 h the levels of IL-1β and NGF in the hindpaw.
A single injection of anti-TNFα antiserum, 1 h before the CFA, at a dose sufficient to reduce the effects of a 100 ng intraplantar injection of TNFα, significantly delayed the onset of the resultant inflammatory hyperalgesia and reduced IL-1β but not NGF levels measured at 24 h.
The elevation of TNFα in inflammation, by virtue of its capacity to induce IL-1β and NGF, may contribute to the initiation of inflammatory hyperalgesia.