Abstract: AIMTo investigate the effects of nocistatin and nocistatin (10～17) on nociceptin in antagonizing endomorphin-1 or endomorphin-2 analgesia in mice. METHODSNocistatin and nocistatin (10～17) were synthesized by solid-phase peptide synthesis method. The mouse tail-flick test was used to assess the pain threshold of the mice and observe the effects of nocistatin and nocistatin (10～17). RESULTSNociceptin was shown to antagonize endomorphin-1 and endomorphin-2 analgesia. Nocistatin or nocistatin (10～17) produced no significant effect on basic pain threshold; however,both of them were found to reverse the effects of nociceptin in antagonizing endomorphin-1 and endomorphin-2 analgesia. CONCLUSIONNocistatin and nocistatin (10～17) were shown to reverse the effects of nociceptin in antagonizing endomorphin-1 and endomorphin-2 analgesia at supraspinal level.