Involvement of interleukin-1 beta, nerve growth factor and prostaglandin E-2 in endotoxin-induced localized inflammatory hyperalgesia

1 Intraplantar endotoxin (ET) injection (1.25 mu g) 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-1 beta (IL-1 beta) 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 mu g 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-1 beta and prostaglandin E-2 (PGE(2)) 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-1 beta, NGF and prostaglandin E-2 (PGE(2)) 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.