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

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-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 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-1β, 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.

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