Lipopolysaccharide, also known as endotoxin (ET), is a major constituent of the outer membrane of the cell wall of most gram negative bacteria. ET is known to cause a number of pathophysiological changes associated with illness including inflammatory pain. The aim of this study is to characterize the peripheral hyperalgesia induced by ET in rats and mice. Different groups of rats and mice received different doses of ET ranging from 0.6 microgram to 40 micrograms dissolved in 50 microliters saline and injected in the plantar area of the left hind legs. All animals were subjected to tail immersion (TF), hot plate (HP) and paw pressure (PP) tests, 2-3 days prior to ET injection and during the following 1-2 days. ET injections produced a dose-dependent decrease in the latencies of the HP and PP tests of the injected leg reaching a maximum decrease of 50-60% of the control with 20-40 micrograms ET at 9 h (rats) and 24 h (mice) after the injection. Almost complete recovery was observed after 24 h in rats and 48 h in mice. TF latencies showed a less but a significant decrease while PP of the opposite leg and all tests in saline-injected animals did not elicit significant variations and served as additional controls. Our results indicate that the use of ET-produced hyperalgesia is a valid model for local and reversible inflammatory pain, with minimal distress to the animal. This model can also be used to study the efficacy of various anti-inflammatory and analgesic drugs and the molecular mechanisms of inflammation induced by bacterial invasion.

No 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.

Classical description of syndromes produced by cutaneous leishmaniasis (CL) does not include sensory manifestations such as pain and/or itching, despite the evident upregulation of proinflammatory cytokines. Using a murine model of CL we report on evident hyperalgesia, as assessed by acute pain tests, and sustained upregulation of interleukin (IL-1beta) and nerve growth factor (NGF). This upregulation, especially that of NGF, may explain the observed hyperalgesia, in the light of recent evidence on the role of cytokines in the sensitization of nerve afferents and the subsequent hyperalgesia.

1 Exposure to midrange ultraviolet radiation (UVB) is known to produce skin in¯ammation similar to sunburn. The aim of this study was to characterize the hyperalgesia and cytokine upregulation induced by UVB and their modulation by antiin¯ammatory cytokines. 2 Acute exposure of the dorsal skin of mice to UVB (200, 250 and 300 mJ cm 2 ) resulted in a dosedependent decrease in the latencies of the hot plate and tail¯ick tests, without evident signs of skin lesions. 3 The observed hyperalgesia displayed a biphasic temporal evolution with an acute phase (3 ± 6 h) and a late (48 ± 96 h) phase. 4 Exposure to UVB (300 mJ cm 2 ) elicited signi®cant upregulation of interleukin (IL)-1b, tumour necrosis factor (TNF)-a and nerve growth factor (NGF), determined by ELISA in the exposed skin. This upregulation was more important during the acute phase of hyperalgesia. 5 Daily treatment of mice, with i.p. injections of either IL-10 or IL-13 (1.5, 7.5 and 15 ng in 100 ml saline) produced a dose-dependent attenuation of the UVB-induced hyperalgesia. 6 Treatment with the highest doses of either IL-10 or IL-13, produced signi®cant attenuation of the levels of the cytokines and NGF by UVB, with relatively more pronounced e ects by IL-13. 7 Acute exposure to moderate amounts of UVB results in a systemic hyperalgesia related to the upregulation of cytokine and NGF levels, since both were prevented by treatment with antiin¯ammatory cytokines.