Endotoxin-induced local inflammation and hyperalgesia in rats and mice: a new model for inflammatory pain

Abstract

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.

Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain

“…Because sEHIs have been shown to possess vascular anti-inflammatory properties, the present study addresses the hypothesis that sEHIs have anti-nociceptive properties in a rat model of LPS-induced local inflammatory hyperalgesia (Kanaan et al, 1996), suggesting that sEHIs might serve as novel anti-inflammatory agents for pain relief. Because sEHIs raise endogenous EET levels by preventing EET degradation, we further hypothesized that exogenous EETs would reduce hyperalgesia when applied directly to the hind paw.…”

Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

“…The cut-off latency time was adjusted to 15 s to prevent tissue injury. The hyperalgesic response in the tailwithdrawal test is generally attributed to the central mechanisms of pain [14,15].…”

“…The anti-nociceptive reaction on the hot-plate is thought to stem from a combination of central and peripheral mechanisms [14]. In this test, the animals were placed individually on a hot-plate (May AHP 0603 Analgesic Hot-plate Commat, Turkey) with the temperature calibrated to 54±3°C.…”

Effects of oxytocin and oxytocin receptor antagonist atosiban on nociception and morphine analgesia in rats

“…The latency to the first sign of paw licking or jump response to avoid the heat was taken as an index of the pain threshold; the cut-off time was 30 s in order to avoid damage to the paw. The antinociceptive response on the HP test is considered to result from a combination of peripheral and central mechanisms 11 .…”