Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat

摘要

The present study examines the effect of PAT (peptide analogue of thymulin) in two rat models of inflammatory hyperalgesia induced by either i.pl. (1.25 μg in 50 μl saline) or i.p. (50 μg in 100 μl) injections of endotoxin ET.Pretreatment with PAT (1, 5 or 25 μg in 100 μl saline, i.p.) decreased, in a dose dependent manner, both mechanical hyperalgesia, determined by the paw pressure (PP) test and thermal hyperalgesia determined by the hot plate (HP), the paw immersion (PI) and the tail flick (TF) tests.Compared to the tripeptides K(D)PT and K(D)PV, known to antagonize interleukin (IL)-1β or IL-1β and PGE2 mechanisms, PAT, at lower dosages, exerted stronger anti-hyperalgesic effects.When compared with the effect of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti-inflammatory drugs (NSAID), PAT demonstrated equal analgesic actions.Pretreatment with PAT, reduced significantly the increased concentration of IL-1β, IL-6, TNF-α and NGF due to i.pl. injection of ET.Injection of i.p. ET produced sickness behaviour characterized by hyperalgesia and fever. Pretreatment with PAT prevented the hyperalgesia and maintained the body temperature within the normal range and was accompanied by a down-regulation of the levels of pro-inflammatory cytokines and PGE2 in the liver.PAT, in all doses used, did not result in any evident changes in the physiological parameters or in the normal behaviour of the rats.The anti-hyperalgesic and anti-inflammatory effects of PAT can be attributed, at least partially, to the down-regulation of pro-inflammatory mediators.