In this study, the role of descending monoaminoergic pathways in the antinociceptive effect of intracerebroventriculary (icv) administered N-carboxymethyl-Phe-Leu (NcPL), inhibitor of neutral endopeptidase, against thermal stimuli induced pain in rats was investigated by icv administering the neurotoxin 6-hydroxydopamine (6-OHDA). Antinociceptive effect of NcPL icv applied in doses of 5, 50 and 500 μg/kg before and 4 days after icv application of 6-OHDA in a dose of 100 μg/animal was evaluated in Tail-immersion test at 55 + 0.5°C 15 and 45 minutes after application. Results on our experiments show that 5 μg/kg of NcPL exerted significant increase in mean latency 45 minutes after application (5.24 ± 0.28 Vs 3.64 ± 0.36 sec., p < 0.01), 50 μg/kg 15 (5.34 ± 0.29 Vs 3.64 ± 0.36, p < 0.01) and 45 minutes (5.53 ± 0.29 Vs 3.64 ± 0.36, p < 0.01) and 500 μg/kg 15 (5.94 ± 0.30 Vs 3.64 ± 0.36, p < 0.001) and 45 minutes after application (5.64 ± 0.29 Vs 3.64 ± 0.36, p < 0.001). Pretreatment with 6-OHDA leads to complete inhibition of antinociceptive effect of NcPL icv applied in old three doses and in both time period after application. That finding prove the role of descending noreadrenergic pathways in the antinociceptive effect of NcPL. Mean latency in all group pretreated with 6-OHDA is not significant different from control indicating that in antinociceptive effect of NcPL may also be included other descending inhibitory pathways.