Melatonin reversal of lipopolysacharides-induced thermal and behavioral hyperalgesia in mice

The perception of pain sensation (threshold), whether local or central, is altered by inflammatory processes. Anti-inflammatory drugs block this by ra ising the pain threshold and by reducing the inflammatory process. Melatoni n is claimed to have anti-inflammatory activity in animal models of acute a nd chronic inflammation. However, it is not known whether melatonin can rev erse the hyperalgesia that is secondary to the inflammation. The present st udy aimed to assess the modulatory effect of melatonin on lipopolysacharide s-induced alteration of pain perception in mice. Central perception of pain was assessed with the tail-flick and hot-plate methods and local hyperalge sia was assessed by noting the animal's reactions such as paw licking and r earing after the intraplantar injection of lipopolysacharides (5 mu g/paw). Local administration (intraplantar) of lipopolysacharides induced hyperalg esia when measured by both central effects and behavioral reactions. Melato nin (5 and 10 mg/kg), like dexamethasone (0.5 mg/kg), given 30 min prior to , and 4 and 8 h after lipopolysacharides (5 mu g/paw) challenge attenuated central and behavioural hyperalgesia. The attenuation of lipopolysacharides -induced hyperalgesia by melatonin was not reversed by naltrexone (4 mg/kg) . in vitro studies showed that melatonin, in concentrations ranging from 10 0 to 1000 nM, suppressed tumor necrosis factor-alpha (TNF-alpha) without af fecting the nitric oxide (NO) release in lipopolysacharides-activated murin e peritoneal macrophages. Taken together, the present results demonstrated that melatonin reverses lipopolysacharides-induced hyperalgesia. (C) 2000 E lsevier Science B.V. All rights reserved.