British Journal of Pharmacology

14 August 1997, Volume 121, Issue 8, Pages 1619 – 1626

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Article
Involvement of interleukin-1beta, nerve growth factor and prostaglandin E2 in endotoxin-induced localized inflammatory hyperalgesia

Bared Safieh-Garabedian1,3, Salim A. Kanaan1, John J. Haddad1, Pamela Abou Jaoude2, Suhayl J. Jabbur2 & Nayef E. Saadé2

1Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon     2Departments of Human Morphology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon    

3Author for correspondence



Keywords
Inflammation;   hyperalgesia;   interleukin-1beta;   nerve growth factor;   prostaglandin E2

Abstract

1   Intraplantar endotoxin (ET) injection (1.25 µg) into the hind paw of rats resulted in a localized inflammatory hyperalgesia, as assessed by paw pressure (PP), paw immersion (PI), tail flick (TF) and hot plate (HP) tests.

2   ET injection resulted in a significant elevation in the levels of interleukin-1beta (IL-1beta) and nerve growth factor (NGF) in the injected foot as compared with the non-injected foot. This increase was attenuated by intraperitoneal injections of dexamethasone (200 and 400 µg kg-1) and to a lesser extent by indomethacin (2 and 8 mg kg-1).

3   The tripeptide Lys-D-Pro-Val, which is known to antagonize IL-1beta and prostaglandin E2 (PGE2) reversed mechanical hyperalgesia, as assessed by the PP test, and reduced significantly thermal hyperalgesia, as assessed by the HP and TF tests.

4   IL-1ra reversed both mechanical (PP) and thermal (PI) nociceptive thresholds tested on the injected leg and significantly reduced thermal hyperalgesia, as assessed by the HP and TF tests.

5   A sheep, anti-mouse NGF antiserum reversed mechanical hyperalgesia (PP test) but had little or no effect on thermal hyperalgesia (PI, HP and TF tests).

6   Our results indicate the importance of IL-1beta, NGF and prostaglandin E2 (PGE2) in the development of ET induced hyperalgesia and the possible existence of different mechanisms underlying thermal and mechanical as well as central and peripheral hyperalgesia.

Received 28 January, 97; Revised 2 May, 97; Accepted 19 May, 97

© Macmillan Publishers Ltd 1997