1. 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 microg in 50 microl saline) or i.p. (50 microg in 100 microl)
injections of
endotoxin ET. 2. Pretreatment with PAT (1, 5 or 25 microg in 100 microl 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. 3. Compared to the tripeptides K(D)PT and K(D)PV, known to antagonize
interleukin (IL)-1beta or IL-1beta and
PGE(2) mechanisms, PAT, at lower dosages, exerted stronger anti-hyperalgesic effects. 4. When compared with the effect of a steroidal (
dexamethasone) and a non-steroidal (
indomethacin) anti-inflammatory drugs (
NSAID), PAT demonstrated equal
analgesic actions. 5. Pretreatment with PAT, reduced significantly the increased concentration of IL-1beta,
IL-6,
TNF-alpha and
NGF due to i.pl. injection of ET. 6. 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
PGE(2) in the liver. 7. PAT, in all doses used, did not result in any evident changes in the physiological parameters or in the normal behaviour of the rats. 8. The anti-hyperalgesic and anti-inflammatory effects of PAT can be attributed, at least partially, to the down-regulation of pro-inflammatory mediators.