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

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‐1β (IL‐1β) 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‐1β 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‐1β, 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.British Journal of Pharmacology (1997) 121 , 1619–1626; doi: 10.1038/sj.bjp.0701313