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

Abstract

1 Intraplantar endotoxin (ET) injection (1.25 mg) into the hind paw of rats resulted in a localized in¯ammatory hyperalgesia, as assessed by paw pressure (PP), paw immersion (PI), tail¯ick (TF) and hot plate (HP) tests. 2 ET injection resulted in a signi®cant elevation in the levels of interleukin-1b (IL-1b) 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 mg kg 71) and to a lesser extent by indomethacin (2 and 8 mg kg 71 ). 3 The tripeptide Lys-D-Pro-Val, which is known to antagonize IL-1b and prostaglandin E 2 (PGE 2 ) reversed mechanical hyperalgesia, as assessed by the PP test, and reduced signi®cantly 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 signi®cantly 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 eect on thermal hyperalgesia (PI, HP and TF tests). 6 Our results indicate the importance of IL-1b, NGF and prostaglandin E 2 (PGE 2 ) in the development of ET induced hyperalgesia and the possible existence of dierent mechanisms underlying thermal and mechanical as well as central and peripheral hyperalgesia.

Nociceptive Effect of Subcutaneously Injected Interleukin-12 Is Mediated by Endothelin (ET) Acting on ETBReceptors in Rats

“…In rats, inflammatory stimuli induce resident cells to release TNF-␣, which in turn activates two pathways: 1) TNF-␣ 3 IL-6 3 IL-1␤ 3 prostaglandins (Cunha et al, 1992), and 2) TNF-␣ 3 cytokine-induced neutrophil chemoattractant 1 (rat IL-8 related chemokine; Lorenzetti et al, 2002) 3 sympathetic amines (Nakamura and Ferreira, 1987;Cunha et al, 1991). The sequential role of cytokines leading to the release of final mediators was further substantiated in rats by Safieh-Garabedian et al (1997) and, more recently, in mice by Cunha et al (2005). Furthermore, cytokines may also stimulate the release of other directly acting mediators, such as endothelin (ET) .…”

Anti-inflammatory and antinociceptive activities of an acid fraction of the seeds of Carpotroche brasiliensis (Raddi) (Flacourtiaceae)

“…Carrageenan-evoked hyperalgesia was quantified in separate groups of animals as a measure of the nociceptive response to a thermal stimulus using the hot-plate test with the temperature adjusted to 51 ± 1ºC (14). The withdrawal latency of each hind paw was determined and hyperalgesia defined as a decrease in the ∆ latency (s) calculated as the difference between carrageenan and saline paw latency times.…”

Movement-evoked hyperalgesia induced by lipopolysaccharides is not suppressed by glucocorticoids

“…Cutaneous hyperalgesia develops following injection of LPS directly into the hindpaw Safieh-Garabedian et al, 1996;Safieh-Garabedian et al, 1997). Cutaneous hyperalgesia clearly involves secretion of pro-inflammatory cytokines (Ferreira et al, 1988;Maier et al, 1993;Watkins etal., 1994c;Rietschel et al, 1994), eicosanoids (O'Neill and Lewis, 1989;Decker, 1990), and reactive oxygen species (Beasley et al, 1991).…”

“…TNF-α and IL-1 are responsible for LPS-induced shock leading to the lethal effects of endotoxemia (Beutler et al, 1985;Tracey et al, 1986). These mediators also participate in tactile hyperalgesia following peripheral injections of LPS (Ferreira et al, 1988;Maier et al, 1993;Watkins et al, 1994c;Rietschel et al, 1994, Safieh-Garabedian et al, 1997. Whether muscle pain and decreases in grip force responses that are produced by endotoxins also result from this same group of inflammatory mediators is not known.…”