ENDOTOXIN-INDUCED LOCAL INFLAMMATION AND HYPERALGESIA IN RATS AND MICE - A NEW MODEL FOR INFLAMMATORY PAIN

Lipopolysaccharide, also known as endotoxin (ET), is a major constitue nt of the outer membrane of the cell wall of most gram negative bacter ia. ET is known to cause a number of pathophysiological changes associ ated with illness including inflammatory pain. The aim of this study i s to characterize the peripheral hyperalgesia induced by ET in rats an d mice. Different groups of rats and mice received different doses of ET ranging from 0.6 mu g to 40 mu g dissolved in 50 mu l saline and in jected in the plantar area of the left hind legs. All animals were sub jected to tail immersion (TF), hot plate (HP) and paw pressure (PP) te sts, 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 mu g 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 significa nt decrease while PP of the opposite leg and all tests in saline-injec ted animals did not elicit significant variations and served as additi onal controls. Our results indicate that the use of ET-produced hypera lgesia is a valid model for local and reversible inflammatory pain, wi th minimal distress to the animal. This model can also be used to stud y the efficacy of various anti-inflammatory and analgesic drugs and th e molecular mechanisms of inflammation induced by bacterial invasion.